CHRONIC PAIN | +80 articles

[mr peabody]

Ketamine a useful alternative for pain relief in hospitals*

by Adam Sturts, MSIV | HPC Live | 18 Feb 2020

Results of a new study indicate continuous infusion ketamine could increase time spent in goal pain and sedation score range and decrease the need for opioids, benzodiazepines, and other analgesics—indicating it could be a reliable alternative for intensive care unit (ICU) patients.

Presented at the Society of Critical Care Medicine’s 49th Annual Critical Care Congress in Orlando, the Effects of Ketamine on Pain, Sedation, and Delirium in the Intensive Care Unit (Ketamine-ICU Study) was designed to address the lack of guidance as to how to use ketamine in the ICU.

“We feel ketamine is a reasonable option especially in those failing traditional sedative and analgesia regimens,” said Christine Groth, PharmD, Clinical Pharmacy Coordinator of the University of Rochester Medical Center.

The Ketamine-ICU study was designed by Groth and the Ketamine-ICU study members as a multicenter, retrospective study evaluating a cohort of 390 adult ICU patients from 25 institutions from 2014-2017. The mean age of the study participants was 52 years, and the length of stay in ICU was 9 days.

Investigators hypothesized a continuous infusion of ketamine would lead to an increased proportion of time spent in goal pain and sedation score range, reduced exposure to other sedatives, and variable effects on delirium.

For the purpose of the analysis, pain and sedation scores and delirium screenings in the 24 hours prior to ketamine were compared to scores and screenings in the first 24 hours and 25 to 48 hours following ketamine administration.

Investigators pointed out there was no difference in median time spent delirious after ketamine initiation. Additionally, results suggest ketamine associated with a significant reduction in opioid, benzodiazepine, propofol and dexmedetomidine requirements.

“Eighty percent of patients were mechanically ventilated and in a fair amount of these patients ketamine was continued through the extubation period, which we thought was interesting,” Groth said.

Of note, 6 percent of participants discontinued participation due to adverse effects. Adverse effects observed in participants included increased secretions, which occurred in 10 percent of patients, and resulted in increased anticholinergic use. Additionally, psychotropic effects were recorded in just 5 percent of patients—however, this study was retrospective and, because of this, these effects may have been underrepresented.

“We definitely need prospective randomized comparative data to really determine its place in therapy as well as the overall safety of this medication,” Groth added.

Ketamine Could Be Useful Alternative for Pain Relief, Sedation in ICU

A fourth-year medical student offers perspective on a study examining the use of ketamine in ICUs being presented at CCC 49 in Orlando, FL as part of HCPLive's Notes from Rounds program.

www.mdmag.com

 

[mr peabody]

Psychedelics may relieve chronic pain via changes in brain neuroplasticity

by Barb Bauer | Psychedelic Science Review | 21 May 2020

Using psychedelics to treat chronic pain understudied yet full of potential.

In the journal Regional Anesthesia and Pain Medicine, researchers from the University of California San Diego have reviewed the psychedelic literature and proposed a mechanism by which psychedelics may be used to relieve chronic pain.

The literature review discusses studies using psychedelics to treat conditions like cluster headaches, migraines, cancer pain, and phantom limb pain. The compounds involved in the studies were psilocybin, LSD, and the LSD analog 2-bromolysergic acid diethylamide.

The authors cover the history of psychedelics, studies on their efficacy, tolerability, and safety, and the chemical classes. In proposing their hypothesis for how psychedelics act as analgesics, the authors reviewed three concepts:

1) The mechanism of action of psychedelics at serotonin receptors (primarily 5-HT2A).

2) The downstream effects of psychedelics in the body leading to modulation of gene expression and inflammation.

3) Changes in brain functional connectivity (FC) brought on by psychedelics.

Psychedelics for chronic pain – making the case

According to the authors, several mechanisms might contribute to the antinociceptive (detection of pain) effects of psychedelics.

Based on the literature, they observed that activating the 5-HT2A receptor (as the classic psychedelics do) causes upregulation (becoming more active) of the genes that are associated with neuroplasticity. The genes that suppress inflammation via tumor necrosis factor alpha (TNF-α) also experience upregulation when the receptor is activated. Therefore, 5-HT2A receptor activation by psychedelics may lead to rewiring in the brain + reduced inflammation = reduced nociception.

The authors explain that studies have shown that over time, acute pain transforms into chronic pain via neuroplasticity. Also, other changes in the structure and function of the nervous system in areas like the spinal cord and the cortex of the brain are involved. It is in this evidence that they find the primary driver of their hypothesis:

"Given the accumulating evidence of altered brain FC in chronic pain states, the ability of psychedelics to disrupt established brain connection patterns is perhaps the most intriguing potential analgesic mechanism for psychedelics."

Based on the scientific evidence overall, the researchers made the following recommendation:

"Given the current state of the opioid epidemic and limited efficacy of non-opioid analgesics, it is time to consider further research on psychedelics as analgesics in order to improve the lives of patients with chronic pain conditions."

What’s next for psychedelics in treating chronic pain?

The authors note that of the 200+ clinical trials examining the effects of psychedelic drugs on health conditions, none are studying how psychedelics impact chronic pain. To fill this gap, they propose two main areas for further investigation: 1) identifying the mechanisms that support psychedelic-induced analgesia and 2) placebo-controlled trials to quantify the effective doses of psychedelics that provide predictable and reliable pain relief.

Psychedelics May Relieve Chronic Pain Via Changes in Brain Neuroplasticity

Using psychedelics to treat chronic pain is understudied yet full of potential.

psychedelicreview.com

 

[mr peabody]

Kratom compound Mitragynine reduces neuropathic pain, study

by Barb Bauer | Psychedelic Science Review | 3 April 2020

Pain was inhibited by an α2-adrenoceptor antagonist and reduced by an α1-adrenoceptor antagonist. Opioid receptors may also be involved in the effects.

Kratom is a species of tree known scientifically as Mitragynia speciosa that grows in Southeast Asia and Africa. There are over 40 compounds in kratom leaves. Some are biologically active, some are not, and the activity of dozens of them is unknown.

Mitragynine (MG) is the primary indole alkaloid in kratom. Studies have shown that it may alleviate pain and aid in reducing alcohol and opioid dependence. The mechanisms for these actions are thought to be mediated through the mu, delta, and kappa opioid receptors. MG also has an affinity for several other receptor types that may be involved in its effects. These include dopamine D2, 5-HT2C, and 5-HT7.

A 2020 study by Foss et al. published in Drug and Alcohol Dependence examined the effects of MG on chemotherapy-induced neuropathic pain in rats. The authors noted that drugs targeting and enhancing adrenergic receptor transmission are often prescribed first for patients with neuropathic pain. From this, they tested whether MG reduced neuropathic pain via activation of α-adrenoceptors (a category of adrenergic receptors).

Study design

To study the effects of MG doses on pain, male rats were divided into groups of eight individuals. They were injected with the cancer medication oxaliplatin, which causes a condition called allodynia. Twenty-four hours later, the rats then received a fixed intraperitoneal (IP) dose of MG at 0, 1, 5, or 10 mg/kg for five days. The allodynia each rat experienced was quantified on days 2 and 5 by measuring their paw withdrawal threshold using Von Frey filaments.

Three antagonists were employed to understand the receptor mechanisms involved in pain relief. Additional groups of 12-16 rats received the following fixed IP doses for six days:

- 5 mg/kg MG + 5 mg/kg yohimbine, an α2-adrenoceptor antagonist
- 5 mg/kg MG + 5 mg/kg prazosin, an α1-adrenoceptor antagonist
- 5 mg/kg MG + 5 mg/kg naltrexone, an opioid antagonist

The mechanical sensitivity of the rats was tested on days 2 and 5 using the Von Frey filaments. An additional test was done on the day after cessation of treatment, day 7.

Finally, the researchers tested the effect of MG on the locomotor activity of rats using an activity chamber. Groups of seven individuals were given 0, 1, 5, 10, or 30 mg/kg IP, and their activity measured for 30 minutes.

Effects of treatment with MG

Effects on pain relief

The data showed that MG reduced the chemotherapy-induced pain in the rats in a dose-dependent manner. Compared to the controls, 10 mg/kg MG reduced the allodynia on days 2 and 5. On day 5, the 5 mg/kg dose of MG also reduced the oxaliplatin-induced allodynia. The 1 mg/kg dose produced a minimal effect on days 2 and 5 compared to the control.

Receptor mechanisms

The allodynia produced by oxaliplatin was reduced by MG. The addition of the antagonists Yohimbe, prazosin, and naltrexone caused significant suppression of MG’s ability to relieve the oxaliplatin-induced pain. These results indicate that MG works to reduce neuropathic pain via activation of α-adrenoreceptors. The authors also suggest that the pain relief was “at least partially dependent on opioid receptor activity,” which is consistent with the published literature.

Effects on locomotor activity

The doses of 1-10 mg/kg of MG did not produce a change in the rat’s locomotor activity. However, the highest 30 mg/kg dose produced a modest but significant increase in activity 10 and 15 minutes after injection. The authors stated that these data did not agree with previous studies published in the literature. They hypothesized this could be because they only recorded the locomotor activity for 30 minutes.

Summary

Overall, the results of this study indicate that MG was effective in relieving chemotherapy-induced neuropathic pain. This effect was inhibited by an α2-adrenoceptor antagonist and reduced by an α1-adrenoceptor antagonist. However, the underlying mechanisms causing these effects remain unclear. The authors hypothesized some possible mechanisms by saying,

"For effects observed here with MG, multiple mechanisms are possible, including direct activation of α-adrenoceptors, as well as indirect activation, through processes such as inhibition of norepinephrine reuptake or catabolism (e.g. blockade of monoamine oxidase or catechol-O-methyltransferase)."

Kratom Compound Mitragynine Reduces Neuropathic Pain, Study Finds

Pain was inhibited by an α2-adrenoceptor antagonist and reduced by an α1-adrenoceptor antagonist. Opioid receptors may also be involved in the effects.

psychedelicreview.com

 

[mr peabody]

Hemp oil effectively treats chronic neuropathic pain: study

by University of New Mexico | Medical Xpress | 20 May 2020

Researchers examine the effectiveness of consuming hemp oil extracted from the whole Cannabis plant using a chronic neuropathic pain animal model. Researchers at The University of New Mexico (UNM) showed that legal Cannabis hemp oil reduced mechanical pain sensitivity 10-fold for several hours in mice with chronic post-operative neuropathic pain.

Distinguished from its still largely criminally prohibited cousin, "hemp" refers to Cannabis plants with less than 0.3 percent tetrahydrocannabinol (THC) per mass. Hemp is now federally legal to produce and consume in most regions throughout the United States (U.S) as a result of the Hemp Farming Act, proposed by the U.S. Congress and signed into law by President Donald Trump in 2018.

This major breakthrough in cannabis prohibition now enables millions of Americans the ability to access a natural, effective, and relatively safe alternative option for treating chronic pain. Conventional pharmacological drugs, namely opioids, are driving the leading form of preventable deaths and conventional medical errors are the third leading cause of death in the U.S.

The University of New Mexico has conducted a series of recent studies testing the effectiveness and safety of consuming the Cannabis plant, but this is the first study measuring the therapeutic potential of legal hemp oil with low THC levels.

"Cannabis plants with low THC are still psychoactive, but tend to result in less psychedelic experiences, while still offering profound and often immediate relief from symptoms such as pain, anxiety, and depression," says co-researcher, Dr. Jacob Miguel Vigil, associate professor in the UNM Psychology Department.

Using a chronic neuropathic pain model that exposes mice to post-operative neuropathic pain equivalent to several years of chronic pain in human clinical patients, the researchers were able to examine how hemp oil influences momentary pain sensitivity to the affected region. For several hours after Cannabis consumption the mice demonstrated effective pain relief, approaching the mechanical pain sensitivity of naïve control mice that did not undergo the surgical operation.

"Our lab utilizes a unique nerve injury model mimicking human neuropathic pain that has allowed demonstration of hemp's reversal of the pain related behavior" said one of the lead investigators, Dr. Karin N. Westlund, Department of Anesthesiology, their article titled "The Therapeutic Effectiveness of Full Spectrum Hemp Oil Using a Chronic Neuropathic Pain Model," published in the journal Life.

Studies in animals can be superior to clinical trials because they circumvent human biases and expectancy effects, or perceptual and cognitive reactions to enrollment in cannabis-themed experiments. Several studies measuring the effects of cannabis in humans observe patients reporting psychedelic experiences, whether or not they received the active cannabis agent, otherwise referred to as the 'placebo effect.'

The study examined the effectiveness of "LyFeBaak" hemp oil, produced by Organic-Energetic Solutions, which has been available for legal purchase in New Mexico since 2019. "We grow hemp that is optimized to potentiate the plants utmost health and vitality through hypermineralization techniques, rather than merely plants that are grown in a state of fight-or-flight, which unfortunately is common in the cannabis industry. These techniques have enabled us to produce hemp products that patients swear are effective for treating dozens of mental and physical health conditions. The new changes in hemp laws are now allowing us to test these claims," adds co-author and hemp grower, Anthony L. Ortiz.

"Hemp plants contain numerous therapeutic constituents that likely contribute to analgesic responses, including terpenes and flavonoids, which in theory, work together like members of a symphony, often described as the entourage effect," says fellow researcher, Jegason P. Diviant. Several clinical investigations have shown that medications based on synthetic cannabis analogues and isolated compounds tend to offer lower reported symptom relief and a greater number of negative side effects as compared to whole plant, or "full-spectrum" Cannabis flower and plant-based extracts.

The authors do caution that few studies exist on the long-term use of hemp oil, due mostly to historical federal prohibition laws in the U.S. "However, this is an extremely exciting time in modern medical discovery, because the average citizen now has legal access to a completely natural and effective medication that can be easily and cheaply produced, simply by sticking a seed in the ground and caring for it as you would any other important part of your life," says Vigil.

Legal Cannabis hemp oil effectively treats chronic neuropathic pain: study

Researchers examine the effectiveness of consuming hemp oil extracted from the whole Cannabis plant using a chronic neuropathic pain animal model. Researchers at The University of New Mexico (UNM) showed that legal Cannabis hemp oil reduced mechanical pain sensitivity 10-fold for several hours...

medicalxpress.com

 

[mr peabody]

Metered-dose cannabis inhaler safe and effective for chronic pain patients

by Paul Armentano | 26 May 2020

The delivery of precise doses of THC via an inhaler is associated with pain mitigation in patients with neuropathy and other complex pain conditions, according to clinical trial data published in the European Journal of Pain.

A team of Israeli researchers conducted a randomized placebo-controlled clinical trial to assess the safety and efficacy of a novel, metered-dose cannabis inhaler in 27 patients with chronic pain. Participants inhaled a precise dose containing either THC (at doses of either 0.5mg or 1mg) or placebo.

They reported: “Both doses, but not the placebo, demonstrated a significant reduction in pain intensity compared with baseline and remained stable for 150-minutes. The 1mg dose showed a significant pain decrease compared to the placebo. Adverse events were mostly mild and resolved spontaneously. There was no evidence of consistent impairments in cognitive performance.”

Authors concluded: “This feasibility trial demonstrated that a metered-dose cannabis inhaler delivered precise and low THC doses that produced a dose-dependent and safe analgesic effect in patients with neuropathic pain/complex-regional pain syndrome (CRPS). Thus, it enables individualization of medical cannabis regimens that can be evaluated pharmacokinetically and pharmacodynamically by accepted pharmaceutical models.”

Prior clinical trials, such as those here and here, have similarly reported that a metered-dose inhaler can deliver precise therapeutic doses of cannabis to pain patients absent any significant adverse effects.

Chronic pain is the most commonly reported qualifying condition among medical cannabis patients enrolled in state-specific access programs. A 2017 literature review by the National Academy of Sciences, Engineering, and Medicine concluded, “There is conclusive or substantial evidence that cannabis or cannabinoids are effective for the treatment of chronic pain in adults.”

An abstract of the study, “Pharmacokinetics, efficacy, and safety of a novel selective-dose cannabis inhaler in patients with chronic pain: A randomized, double-blinded, placebo-controlled trial,” is online here. Additional information regarding cannabinoids and pain appears online here.

Clinical Trial: Cannabinoid Administration Via a Metered-Dose Inhaler Is Safe and Effective for Chronic Pain Patients - NORML

Researchers reported: "Both doses, but not the placebo, demonstrated a significant reduction in pain intensity."

blog.norml.org

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[mr peabody]

Cannabis associated with reduced opioid use, prolonged benefits in pain patients

by NORML | 19 June, 2020

The daily use of cannabis by patients with chronic pain conditions is associated with prolonged improvements in pain management and subjects’ overall quality of life, as well as sustained reductions in the use of opioids, according to longitudinal data published in the journal Pain Medicine.

A team of Canadian researchers assessed the short-term and long-term impacts of medical cannabis treatment in 751 chronic pain subjects. Participants in the study consumed cannabis daily for a period of 12 months. Sixty percent of subjects reported having no previous experience with cannabis prior to their involvement in the study.

Investigators observed clinically significant improvements in patients’ pain severity “as early as one month after initiating treatment, and these improvements were maintained over the course of the 12-month observation period.” In addition, patients’ “reported frequencies of fatigue, headaches, feelings of anxiety, and nausea decreased compared with baseline.”

Patients who were taking opioids prior to their enrollment in the study reduced their daily intake of opiates over the trial period — a finding that is consistent with those of several other longitudinal studies, such as those here, here, and here. Investigators observed initial reductions in patients’ opioid consumption at three months. Patients further reduced their opioid intake at six months and again at twelve months.

Authors concluded, “Taken together, the results of this study add to the cumulative evidence in support of plant-based MC (medical cannabis) as a safe and effective treatment option and potential opioid substitute or augmentation therapy for the management of chronic pain symptomatology and quality of life.”

Commenting on the study’s findings, NORML Deputy Director Paul Armentano said, “These outcomes add to the growing body of literature supportive of the therapeutic use of cannabis as an opioid-sparing analgesic agent.”

The study, Medical cannabis for the management of pain and quality of life in chronic pain patients: A prospective observational study, appears in Pain Medicine.

Study: Cannabis Associated with Reduced Opioid Use, Prolonged Benefits in Pain Patients - NORML

“Taken together, the results of this study add to the cumulative evidence in support of plant-based MC (medical cannabis) as a safe and effective treatment option and potential opioid substitute or augmentation therapy for the management of chronic pain symptomatology and quality of life.”

norml.org

 

[mr peabody]

Long-lasting analgesic effects of Changa + ground seeds of Peganum harmala*

Genis Ona, Sebastian Troncoso

Pain is the most prevalent symptom of a health condition, and it is inappropriately treated in many cases. Here, we present a case report in which we observe a long-lasting analgesic effect produced by Changa, a psychedelic drug that contains the psychoactive N,N-dimethyltryptamine and ground seeds of Peganum harmala, which are rich inβ-carbolines. A long-lasting analgesic effect after the use of changa was reported. We suggest that both pharmacological and non-pharmacological factors could be involved. These findings offer preliminary evidence of the analgesic effect of Changa, but due to its complex pharmacological actions, involving many neurotransmitter systems, further research is needed in order to establish the specific mechanisms at work.

The intense psychedelic effects of Changa limit its application in clinical contexts. However, the case reported here suggests that changa can produce a long-lasting analgesic effect, involving a combination of mood-enhancing effects; other psychological factors; an interaction with several neurotransmitter systems; and anti-inflammatory, neuro-protective, and plasticity-promoting actions. Remarkably, Changa could offer pain treatment that targets multiple monoamine neurotransmitters.

*From the study here:

https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwjr9ZWO_LvqAhXDYjUKHaxoDG0QFjADegQIAxAB&url=https%3A%2F%2Fakjournals.com%2Fdownloadpdf%2Fjournals%2F2054%2F3%2F1%2Farticle-p7.pdf&usg=AOvVaw2yi7bVPlE_iO91ROk-f4Fu

 

[mr peabody]

Cannabis helping those with Peripheral Neuropathy

Psychedelic Times Staff

A new study reports that cannabis can help people manage pain from peripheral neuropathy, a type of nerve damage that causes pain in the extremities of the body.

One man shared his experience using the diabetes medication Lyrica — he noted that it made him feel numb, and that he had lost all sensation in his body after taking it. Another man with idiopathic neuropathy, who’d been managing pain in his calves and feet for over twenty years, had been prescribed Lyrica for ten of them. While he had already decreased his dosage in the recent years with the help of a MedTronics unit, he wanted to stop the medication completely because of its side effects and so was interested in other options. Another woman explained that she just didn’t want to take prescription pain medication because she was worried about getting addicted.

While their concerns varied, what unified the people in the comments was their desire to find another solution, and this particular study was providing an alternative: cannabis. Cannabis has been shown to relieve many types of pain, but several studies in the last decade have focused specifically on the different roles that THC and CBD may play in treating the particular pain caused by neuropathy. While the exact mechanics are unknown, it seems like both these cannabinoids have an important part to play in helping people live without crippling pain.

The pain of Peripheral Neuropathy

Peripheral neuropathy is caused by damage to neurons in the peripheral nervous system, particularly in extremities such as the hands and feet. This damage usually manifests as a painful tingling sensation, which can either occur in multiple areas or can affect only a single neuron. Neuropathy is caused by many things, including chemical exposure, infectious diseases, or chronic diseases such as diabetes (in fact, 60 to 70% of people with diabetes have some sort of nerve damage).

The peripheral nervous system extends through most of the body and extremities.

Because peripheral neuropathy is so often caused by another condition such as HIV, cancer, or diabetes, this makes the stress of neuropathic pain all the more upsetting, because it occurs on top of the symptoms of pre-existing conditions. In another comment in the University of Glasgow article, a woman with HIV shared that her foot pain from neuropathy kept her awake at night. Another example of this would be a close friend of mine who was diagnosed with cancer and was later diagnosed with peripheral neuropathy caused by his chemotherapy. People dealing with diseases like these are likely already dealing with nausea, exhaustion, depression, and general discomfort. Add peripheral neuropathy to the mix, and they can’t even walk to the bathroom without feeling painful pins and needles.

How cannabis can help manage pain

There have been several studies that show cannabis’ efficacy at treating and reducing pain, including a 2007 study published in Neurology that showed its ability to treat neuropathic pain associated with HIV. However, this cannabis research has mostly focused on delta-9-THC, the cannabinoid responsible for cannabis’ psychoactive high. But now we’re understanding that the cannabinoid CBD plays just as large a role in the treatment of pain as THC.

Cannabis produces a much higher ratio of THC to CBD, but when cannabis is refined into oil, individual cannabinoids like THC and CBD can be isolated. We know that both THC and CBD play a role in relieving pain, and we also know that THC works better with CBD than without. However, researchers are still looking into the mechanism of how exactly this works. One line of inquiry notes that the body’s natural endocannabinoid system (which is related to several functions including appetite, memory, pain, and mood) runs parallel in some respects to the endorphin system, which has a well-established role in pain management. Researchers from the Neurology study on HIV-associated neuropathy offered another idea, pointing out that the reduction in pain from using cannabis could be attributed to relaxation or the psychedelic high.

Regardless of how exactly it works, the continuously growing number of studies and anecdotal accounts of people who get relief from peripheral neuropathy by using cannabis — whether by smoking, vaporizing, ingesting, or using an oral spray like in the University of Glasgow study — suggests that cannabis and its main ingredients can play a major role in pain management.

Stepping forward to accept cannabis treatment

Luckily, the future of cannabis therapy is bright. The people of the US have never been more supportive of medical and recreational cannabis use, and even the federal government is coming around to the truth about cannabis. Even though some states are passing laws supporting the rights of insurance companies not to reimburse for cannabis medicines, the much greater trend throughout the country is very heartening. As more and more money is made in states that have legalized cannabis and those taxes are collected by the state governments, it’s very likely that the monetary benefits will trump conventional morality politics. We can only hope that happens (and work together to make it happen), so people no longer have to risk dangerous prescription side effects just to find relief from their pain.

How Cannabis Helps People with Peripheral Neuropathy Manage Pain and Get Back on Their Feet - Psychedelic Times

For people who suffer from peripheral neuropathy, cannabis has shown to be effective at managing pain without the harmful side effects of conventional medications.

psychedelictimes.com

 

[mr peabody]

IV ketamine infusions for acute pain management

by Steven Cohen, MD | HCP Live

The American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists have released consensus guidelines on the use of intravenous ketamine for the management of acute pain.

“The use of ketamine for chronic pain has skyrocketed, and because it is an off-label use of a generic drug, there has not been FDA oversight. This has led to a wide range of indications, and lack of standardization regarding indications, contraindications and dosing,” Steven Cohen, a professor of anesthesiology and critical care medicine at the Johns Hopkins University School of Medicine, and a leading author of the new guidelines, told MD Magazine. "These guidelines have tried to provide a framework for major issues for which there is no consensus."

The guidelines were developed to cover the following areas, all of which the group of authors was able to reach consensus on:

- Indications and contraindications for acute pain and whether they differ from those for chronic pain.
- Evidence for the use of ketamine as an adjunct to opioid-based therapy.
- Evidence supporting patient-controlled ketamine analgesia.
- Use of nonparenteral forms of ketamine.
- Subanesthetic dosage range and whether the evidence supports those dosages for acute pain.

The guidelines note there is a variety of supporting evidence for the use of ketamine as a stand-alone option, adjunct to opioids. The contraindications agreed upon for acute are similar
to those for chronic pain, in part, according to Cohen and colleagues, due to dosing range similarities.

“Larger studies evaluating different acute pain conditions are needed to enhance patient selection, determine the effectiveness of nonparenteral ketamine alternatives, define optimal treatment parameters, and develop protocols optimizing safety and access to care,” they wrote.

"Ultimately, the guidelines sought to clear up the confusion about the therapy, which is a result of different regulations at the state level. Maryland, for example, considers ketamine an anesthetic, so nurses cannot push for its use, thus the guidelines try to define what is an anesthetic or subanesthetic dosage," Cohen said.

"There is confusion among healthcare providers, patients, regulators and institutions about who might benefit from infusions, and how can they safely and effectively be implemented," he explained. "Considerations include how much medication should be given, and over what time period, how should patients be monitored, whether there is any benefit from non-parenteral forms of ketamine, and how to constitute a response."

As far as acute pain is concerned, it appears clear that ketamine is available to play a role. Cohen, as the Director of Pain Research at the Walter Reed National Military Medical Center and a retired army colonel, agrees that there is definitely a place for ketamine in its management, including military implications.

"Ketamine can be used as a stand-alone drug, or in conjunction with opioids, in people who are opioid-tolerant," he said. "Because the total dosage is likely to be less than that administered for chronic pain—which may require multiple infusions—there may also be less of certain side effects."

With questions abound regarding the best pain management strategies, ketamine infusions, while a treatment option for decades, have recently gained momentum due in part to the ongoing national opioid crisis. That widespread use is what prompted the need for further guidance.

“At this point, we have an opiate crisis in this country,” said Steven P. Levine, MD, the founder and CEO of Actify Neurotherapies. “Opiates themselves are not very effective for treating chronic pain, and then we have the problems of addiction and abuse and the difficulties people have with getting off of these medicines once they start them, and leading to illicit drug use.”

Levine's Actify Neurotherapies works closely with patients that have experiences with long-term opioid use, and for him, ketamine, in addition to its role in treating things like depression and post-traumatic stress disorder (PTSD) and obsessive-compulsive disorder (OCD), has proven to be a very effective pain medication.

“Prescriptions for opiates are going down, but the conditions that require pain treatments haven't gone anywhere,” Levine said. “People still continue to struggle with chronic pain, chronic migraine, fibromyalgia—the same conditions that people were prescribed opiates for, we now need another solution. We wind up seeing many patients who either are currently on opiates or have a chronic pain condition that might otherwise have been treated with opiates, and they're looking for an alternative. So for many of these folks, ketamine can provide that alternative.”

Currently, the US Food and Drug Administration (FDA) classifies IV ketamine as an anesthetic agent for diagnostic and surgical procedures. Recently, the FDA has focused much of its efforts to mitigate the use of opioids on increasing the ease of approval for abuse-deterrent generic opioids. The agency produced guidelines on opioid generics in November 2017.

“Our goal is to decrease the rate of new addiction, unnecessary legitimate and especially illicit use of opioids,” FDA Commissioner Scott Gottlieb, MD, said at the time. “Rather, this is an effort designed to encourage the shift—only when opioids are clinically appropriate—from existing, easily abused products to those that are harder to manipulate."

Guidelines for Use of IV Ketamine Infusions for Acute Pain Management Released

The guidelines included indications and contraindications, evidence supporting its use, and the use of nonparenteral forms of ketamine.

www.hcplive.com

 

[mr peabody]

How ketamine infusions helped me

by Madora Pennington | PAIN NEWS NETWORK | 19 Aug 2020

Berkley Jones is a tough lady. Already a nurse, she joined the U.S. Air Force in her late 30’s, even though she had never run a mile in her life. She worked hard, made it through boot camp and went directly into officer training.

Her life changed after an allergic reaction so severe it required hospitalization. Berkeley never felt the same. Aching and tired, an immunologist diagnosed her with fibromyalgia. Berkley powered on.

Then, during a training exercise that simulated medical scenarios that might happen from a nuclear attack, she severely injured her arm. She awoke after surgery with her arm swollen to five times its normal size and feeling like it was on fire. The pain was unbearable. This was the beginning of her life with Complex Regional Pain Syndrome (CRPS).

For the next six years, her life was consumed by pain. Berkley tried everything doctors recommended. Nothing eased her agony. Wheelchair-bound, she left the military. “I basically stayed in bed most of the time. I was very depressed and in pain,” she recalls.

Berkley heard of ketamine from a friend, looked around and was accepted into a ketamine for CRPS study. She checked into the hospital for 5 days of intravenous ketamine infusions. The results were life-changing.

“By the end of the study I was able to use a cane instead of a wheelchair. I was able to get out of bed and my pain was down to livable levels,” she says.

Berkley went on to write a book, “Ketamine Infusions: A Patient's Guide” and organized Facebook groups to educate patients and doctors about ketamine.

From anesthetic to party drug

Ketamine has become a trendy new treatment for pain and depression, but it’s actually been around for decades. Chemists first discovered ketamine in 1956. By the 1960s, it was in widespread use as an anesthetic, from veterinary offices to battlefields. Ketamine is only approved by the FDA for depression, anesthesia and post-surgical acute pain — which makes its use as a treatment for chronic pain off-label.

Ketamine is not an opioid and does not suppress breathing, making it relatively safe to use. But it does produce an unusual state of dissociation. Patients appear awake, but are often unable to respond to sensory input.

Because the experience is similar to psychosis (delirium, delusions or hallucinations), ketamine also became an underground party drug.

More and more uses are being found for this very unique compound. Ketamine triggers production of glutamate in the brain, which makes connections in the brain regrow. Cognition and mood improve as the brain gets a reboot from the damage of long-term stress that leads to excessive negative thoughts and feelings.

For chronic pain sufferers, ketamine temporarily reverses “central sensitization,” where the brain and spinal nerves receive so much pain input, they go off kilter and the slightest touch becomes painful. This can get so bad that some chronic pain sufferers come to find odors, light and sound extremely painful. Brain fog, poor memory, poor concentration and intense anxiety also happen as part of this cycle of pain overload.

Low dose ketamine

While hospitals treat chronic pain patients with multi-day, high dose infusions of ketamine, outpatient clinics have sprouted up around the country, offering less intense treatment with lower doses.

I began seeing anesthesiologist Dr. David Mahjoubi, of Ketamine Healing Clinic of Los Angeles this year. My foot was very swollen, weeks after surgery. I was looking for a way to reduce the inflammation without stopping the healing process, as ice, NSAIDs and steroids tend to do. I was fortunate to get an appointment, as some LA clinics have a two-year waiting list for infusions.

Dr. Mahjoubi explained ketamine to me this way: “It increases connections between brain cells, thus ‘rewiring’ brain circuitry. Ketamine also blocks pain receptors called NMDA. This is the mechanism for blocking pain. For persons with PTSD, the trauma seems to get processed in a mild, non-troubling way. Ketamine separates one from their anxiety or depression. A ‘release’ is how patients commonly describe it.”

In Dr. Mahjoubi’s experience, ketamine infusions multiple days in a row can be a bit tough. Spreading them out over several weeks can still get good results. It depends on the individual and the amount of relief they receive.

I was afraid to try ketamine, but agreed to a low dose, one-hour infusion. The swelling in my foot dramatically improved. Chronic, low-grade discomfort along my spine also disappeared. I felt emotional relief from past trauma, from pain and other life experiences.

I continued with one low dose infusion every few weeks. I don’t like the experience of the infusion, but it has been well worth it.

I was relieved of minor aches and able to increase my exercise. I did not feel terror when pain kicked in. Sometimes the pain just floated away.

I no longer feared my physical therapist touching my neck, and noticed I was enjoying it. My mood improved and I felt smarter. My ability to concentrate and remember improved.

My neighbor’s annoying dog sounded like he was a few houses away, not barking inside my head.

Madora Pennington getting a ketamine infusion

I felt more connected with others and more accepting of life — less anxious, less terrorized, less inclined to ruminate after every infusion.

I do tend to have fatigue or short periods of intense emotion, which is not unusual. For me, this is just hard work on my health, like going to physical therapy.

Treatment for depression

Tara Dillon, a nurse practitioner, opened Happier You, a ketamine clinic in Columbus, Ohio, after infusions helped her 20-year struggle with depression. She’s had good results treating patients with psychiatric complaints, such as depression, anxiety, and bipolar disorder.

“It's well-known that pain and psychiatric diagnoses, particularly depression, tend to coincide. Patients often report physical improvements such as relief from IBS, improved sleep, or increased energy after ketamine therapy,” she explained. “While everyone is nervous for the first infusion, since they don't know what to expect, most patients end up enjoying the experience.”

Tara usually starts with a low dose of 0.5mg ketamine over 40 minutes, but will titrate up depending on how a patient responds. The most common side effect is mild nausea. Ketamine is not a cure for chronic pain, and it takes time to have an effect.

“For me, ketamine never kicks in immediately. Some people get relief in the first week. It takes at least two weeks and for some, like me, it can take 3 to 4 weeks,” says Berkley Jones. “Once it does kick in, I usually have low pain levels for about 6 to 8 weeks and then they start to climb again. Sometimes overnight the pain comes back excruciating, but the majority of the time it’s a slow increase in my pain back to where it was.”

Unfortunately, insurance won’t always cover ketamine. While the drug itself is cheap, the infusions are expensive because patients must be monitored. That is a real shame, as high-impact chronic pain affects 20 million adults in the United States. This is terrible burden not only to the sufferer, but to their loved ones and the community. Perhaps this will change if and when ketamine is FDA approved as a treatment for chronic pain.

Madora Pennington lives with Ehlers-Danlos Syndrome. Sher writes about EDS and life after disability at LessFlexible.com. Her work has also been featured in the Los Angeles Times.

How Ketamine Infusions Helped Me — Pain News Network

By Madora Pennington, PNN Columnist Berkley Jones is a tough lady. Already a nurse, she joined the U.S. Air Force in her late 30’s, even though she had never run a mile in her life. She worked hard, made it through boot camp and went directly into officer training. Her life changed after an allerg

www.painnewsnetwork.org

 

[mr peabody]

Pain and Psychedelics Part I: Suffering in the East and West

SPIRIT PHARMACIST | 10 Dec 2019

This blog is first installment in a 2 part series discussing pain and psychedelics. We’ll begin with an overview of approaches to pain from Western and Eastern perspectives as well as a discussion of where ketamine and serotonergic psychedelics (MDMA, psilocybin, LSD, mescaline, and ayahuasca) fit. In Part II we’ll discuss interactions between pain medications and psychedelics in the context of psychedelic healing.

Pain and suffering

Pain is a complex phenomenon and is closely associated with suffering. Pain is commonly thought to be experienced from a physical source, such as when we stub a toe, although can also be experienced mentally or socially (psychological pain). Important to this discussion, mental illness and pain often walk hand in hand, with one affecting the other and vice versa.

Pain is not equal to suffering despite how closely they normally cluster together. Pain is caused by an uncomfortable physical or mental stimulus (social exclusion), whereas suffering is a psychological reaction to the uncomfortable stimulus. So while pain can be physical or mental, suffering is always a psychological phenomenon. Common assessments of the subjective experience of pain, such as scales that use numeric pictograms as shown below, seem to conflate pain and suffering as the pictures relate to subjective emotional states of suffering rather than objective intensity of physical stimuli. Indeed, subjective ‘pain scales’ have been the subject of intense controversy as their incorporation as a ‘vital sign’ to be measured along with objective measures as heart rate, respiratory rate, blood pressure, or temperature has likely contributed to the current opioid epidemic.

Suffering in the West, Suffering in the East

The pursuit of relief of suffering or escape from suffering is thematically central to both the practice of Western medicine as well as Eastern religious teachings such as Buddhism or Hinduism.

In Western medicine, suffering from pain is relieved via either removing the source of pain (physical therapy or surgery) or by pharmacologic means like pain medication. Pain medication may serve to reduce pain signaling pathways in the peripheral nervous system (PNS) and/or central nervous systems (CNS). Some pain medications are thought to mainly act peripherally (e.g. ibuprofen) and primarily work to reduce pain signaling pathways to the brain. Others, such as opioids or acetaminophen, are active in the CNS and modulates our perception of suffering (amongst other mechanisms such as blockade of pain signals in the spinal cord). Anatomically, it appears there is significant overlap in the regions of the brain that are responsive to physical and emotional pain (there are also differences). Pain medications such as opioids temporarily block emotional perceptions of suffering without distinction of emotional and physical sources. It is recognized that psychological factors and the environment play a large role in the perception and maintenance of chronic pain. Changing trends in the management of chronic pain have allowed subjective experiences of suffering to drive prescribing of opioids and has led to epidemic addiction and overdose deaths in the United States, resulting in declaration of an official public health crisis.

Parallel epidemics in obesity, sedentary lifestyles, depression, and anxiety have taken a toll on the health of Americans leaving them with more pain. It is interesting to consider what role environmental factors or social epidemics such as loneliness, disconnection, and environmental collapse could be having in driving increasing opioid use beyond increased access to opioids. This is of particular interest to this discussion as psychedelics are sometimes touted as agents that could serve an important role in alleviating these social epidemics. Whatever the precipitating factors, it’s apparent that the approach of allowing suffering to drive delivery of potent CNS depressant medication has only exacerbated suffering.

While Buddhism or Hinduism are conceived of as religions, the transcendental meditation practices they offer may also be conceptualized like a doctor with a remedy to escape suffering rather than a philosopher or religious scholar explaining the nature of reality. In these teachings, there is no attempt to remove sources of pain and instead the focus is on the relinquishing of attachments, renunciation of concepts like ‘self’ and ‘other’, as well as desires or beliefs that cause us suffering. The methods for this involve meditation or other practices that quiet and calm the mind. The line of thinking goes that if you realize that your desire to avoid pain is creating an experience of suffering and are able to psychologically detach from the desire to not have pain, then despite pain existing your consciousness can be free of suffering.

Psychedelics: Perspective from the West

Psychedelics are externalities, drugs that are ingested, and serotonergic psychedelics have effects that modulate our response to pain. From a biological perspective, psychedelics may be seen as consistent with existing Western medicines as they are therapeutic solutions that work by changing emotional responsiveness to pain, providing vasoconstriction to relieve headaches, or modifying inflammatory processes that drive painful conditions.

Ketamine

Ketamine currently has more data and evidence of benefit in both mood disorders and pain conditions than serotonergic psychedelics. This is probably true for a number of reasons: Ketamine’s availability as a legal drug and use is anesthesia incentivizes research as an analgesic. Reasonably so, ketamine may be tried for mental health or pain conditions before attempting use of serotonergic psychedelics.

Ketamine is available in either racemic (ketamine) or S-isomer (esketamine) formulations and esketamine is thought to be 4x as potent as an analgesic. Ketamine blocks the N-methyl-D-aspartate (NMDA) glutamate receptor as well as modulates opioid neurocircuitry. This leads to dissociative and analgesic effects and can result in opioid-sparing effects, or reduction in amounts of opioid medication needed to be effective. NMDA receptors are implicated in the adaptation of neuronal pathways and ketamine may be able to prevent the conversion of acute injury to chronic pain or reduce hyperalgesia.

However, daily use of ketamine for chronic pain is currently lacking evidence of benefit and is limited by neurocognitive effects, potential for tolerance or habituation, and lower urinary tract symptoms (LUTS). While ketamine is oftentimes used for opioid-sparing in advanced illness or for analgesia around the time of surgery, it is not very suitable to be used on a frequently on a long term basis.

Serotonergic psychedelics

Existing serotonergic medications such as antidepressants are already known to be helpful for pain conditions, supporting the investigation and development of other serotonergic drugs such as psychedelics in the treatment of pain. It is important to note in this discussion that serotonergic psychedelics (MDMA, psilocybin, LSD, mescaline, ayahuasca) have never been formally studied purely for pain conditions in humans. However, pain and mental illness frequently coexist in a bidirectional relationship with one able to directly affect the other, bolstering the position that psychedelics may be effective for pain conditions.

Mechanistically, 5HT2A receptor stimulation is common to psychedelic effects of serotonergic psychedelics (LSD, mescaline, psilocybin, MDMA, ayahuasca). It also appears that decreasing the availability of 5HT2A receptors can decrease responses to tonic (but not acute) pain. When serotonergic psychedelics bind 5HT2A receptors they produce a rapid decrease in the availability of the 5HT2A receptor, which has been linked to improvements in anxiety, depression, and pain. Serotonin 2A receptor (5HT2A) activation likely modulates the activity of the amygdala as well as other subcortical parts of the brain. These more ancient parts of the brain are known to be involved with emotion as well as pain processing, and could lead to a lessened experience of suffering.

Psychedelics are also accruing data that support they have anti-inflammatory effects. Psychological stressors can activate our hypothalamic-pituitary (HPA) axis leading to production of Cortisol Releasing Factor (CRF). Release of CRF can sensitize our 5HT2A receptors, which may heighten anxious, depressive, or pain responses. Particularly with the phenethylamine psychedelic R-DOI, there is an emerging body of literature supporting that even sub-perceptual doses can potently decrease inflammatory immune responses such as production of the pro-inflammatory cytokine TNF-α. Recently, these results have been extended to inflammatory airway disease such as asthma as well as cardiovascular inflammatory disease such as atherosclerosis. These observations are preliminary and have only tested in animal models thus far, although may carry far reaching therapeutic implications. Drugs aimed at blocking effects of TNF-α are already on the market for treatment of painful autoimmune conditions such as rheumatoid arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, and others. Moreover, inflammatory cardiovascular disease remains a large contributor to illness and death in Western societies and drugs that are effective in reversing or stabilizing progression of illness are frequently ‘blockbuster’ drugs.

Psychedelics: Perspective from the East

The term psychedelic means ‘mind-manifesting’ and use of psychedelics for healing purposes often involves going deeper into ourselves than we ever have previously, often being likened to the superiority of using a telescope to peak at the cosmos opposed to the naked eye. In the sense that psychedelics have the potential for deep experiences of Self, they seem aligned with Buddhist or Hindu teachings of searching for answers within using tools like meditation. While controversial in persons devoted to Eastern religions, it appears that psychedelics may be powerful tools for accessing deep meditative states and enhancing abilities to practice meditation or mindfulness.
Psychedelic phenomena in safe and controlled environments can offer a taste of the mystical in which our consciousness exists in an ineffable place outside of time and space, where the drop has returned to the ocean and boundlessness is felt. In short, a direct experience in which the concepts of ‘Self’ and ‘Other’ are inapplicable. In these non-dual experiences the sense of self or ‘ego’ is partially or completely dissolved. Many mindfulness enthusiasts are using psychedelics to deepen or enhance their meditation practices on their spiritual quest towards enlightenment and psychedelics seem to enhance mindfulness practices.

Significant overlap exists in the neurobiological correlates of mystical experiences, ego-dissolution, transcendental meditation, and mindfulness-based capacities. A set of functionally connected brain circuits called the Default Mode Network (DMN) or task-negative network is active when the brain is at rest. Hyperactivity of portions of the DMN has been linked with mind-wandering or the ever-churning ‘monkey brain’. Additionally, dysfunction of the DMN is associated with several types of psychiatric illness. During psychedelic experiences, the activity of the DMN is diminished, which is correlated with experiences of ego-dissolution and mystical experiences. Persons adept at meditation, appear to be able to reduce the activity of the DMN through meditative practice and many of the brain changes seen in these states are similar to those observed in psychedelic experiences.

While there are similarities between deep meditative states and mystical psychedelic experiences, psychedelics may be best thought of as tools to enhance mindfulness and meditation or be practiced alongside them opposed to tools to replace traditional mindfulness based practices. It seems that psychedelics can enhance mindfulness related capacities. However, when 8 weeks of mindfulness training was compared to 4 ayahuasca sessions, it was found that the mindfulness training enhanced mindfulness in a global degree whereas ayahuasca only enhanced the mindfulness domain of acceptance. A recent trial of psilocybin compared with placebo in a 5 day mindfulness retreat, found more enduring and lasting positive effects in the psilocybin group. Additionally, it was observed that approaching and utilizing mindfulness or meditative related techniques may reduce anxiety or other adverse effects of psilocybin, suggesting that mindfulness could be an important aspect of ‘set & setting’ in creating optimal psychedelic experiences.

Psychedelic lessons on pain

Psychedelics are already being studied and seem helpful for several types of mental suffering; PTSD, anxiety associated with life-threatening illness, treatment resistant depression, and substance use disorders to name just a few. The picture that’s beginning to emerge is that psychedelics have the ability to reduce suffering associated with a variety of pathologies and precipitating experiences. It’s unlikely that suffering could be completely eradicated with psychedelics as this would equate a mystical psychedelic experience with attainment of enlightenment, although may present the “opportunity to transform flashes of illumination into abiding light” when focus and intention is brought to the period of integration post-experience.

All of this begs many unanswered questions on what could be learned from a psychedelic experience in a person with chronic pain?

Perhaps the experience would serve as a proof of concept that pain can exist without suffering…
Perhaps insight into lifestyle factors that keep them in pain could be realized…
Perhaps a vigor could ignited to change the circumstances that trap us in pain…
Perhaps there is a strong attachment to being in pain as it has become a part of the ego’s identity that could be dissolved and subsequently restructured…
Perhaps restoration of a sense of connectedness could alleviate drivers of mental pain…
Perhaps there is an unbeknownst psychospiritual aspect to their pain that could be healed…
Perhaps frequent use of small doses (microdosing) psychedelics combined with meditation could be effective in managing pain conditions…

Part II (below)

But what about traditional pain remedies? Do they complement psychedelic approaches or do they hinder them? Are they dangerous to combine with psychedelics or benign? At this point we’ll leave the philosophical musings on pain and suffering behind and discuss potential interactions between pain medications and serotonergic psychedelics in the second part of this article, Pain & Psychedelics Part II: Drug Interactions with Analgesics.

Pain & Psychedelics Part I: Suffering in the East & West — Spirit Pharmacist

This blog is first installment in a 2 part series discussing pain and psychedelics. We’ll begin with an overview of approaches to pain from Western and Eastern perspectives as well as a discussion of where ketamine and serotonergic psychedelics (MDMA, psilocybin, LSD, mescaline, and ayahuasca) fit.

www.spiritpharmacist.com

​

 

[mr peabody]

Pain and Psychedelics Part II: Drug Interactions with Analgesics

SPIRIT PHARMACIST | 10 Dec 2019

This is the second of two installments on pain and psychedelics. In the first installment or Part I (above), I cover mechanisms of psychedelic action in the context of pain, suffering and philosophy. In this installment I cover drug interactions with different classes of analgesics.

Pain and analgesics: Psychedelic healing, set, and setting

There are many different types of analgesics and pain medications available, each of which has different mechanisms, effects, risks, and interactions with psychedelics. Therefore, we’ll take a class by class approach in this guide. Generally speaking, psychedelic healing works via the heightening of senses, expression or feeling of emotion, and (hopefully) resolution of repressed emotions. Pain relievers or analgesics are drugs that act to suppress pain signals or modulate emotions in a way that suffering is decreased. From this perspective, there is a possibility for counterproductive effects between analgesics and psychedelic-assisted psychotherapy. Counterproductive effects may be further increased by agents that have strong effects in the Central Nervous System (CNS) such as opioids. On the flip side, analgesic agents may increase physical comfort and reduce sympathetic nervous system (fight or flight) arousal due to painful conditions. This could confer beneficial effects on user ‘set’ and the depth of their experience.

When pain conditions are present, the psychedelic user should inquire into and reflect upon any drug or non-drug based modifications that would preserve user ‘set’ or improve user ‘setting’. Adjustments can be made to the physical setting, such as allowing an individual with orthopedic hip and knee injuries to use a comfortable chair to sit in opposed to having them sit on the ground. Many pain medications have the tendency to cause physical or psychological dependence. Discontinuing pain medication may be so damaging to user ‘set’ that they aren’t able to actively participate in their experience. For example, if the user has advanced illness or severe chronic pain (e.g. cancer) it may not be reasonable (due to physical and psychological dependence as well as medical necessity) to discontinue opioid or other pain medication. For others, use of pain medication may be problematic or unwanted. They may be approaching psychedelics in hopes of using less or stopping the use of pain medications. In these cases substance use treatment mind sets may improve outcomes and stopping use of pain medication may be intentional. In most cases (with the exception of ibogaine and ayahuasca which harbor severe physical risks in combination with analgesics), use of pain medication is primarily a risk vs. benefit decision the user can assess based upon their pain condition and goals of analgesic use. A comprehensive assessment of pain conditions as well as their treatments is an essential part of preparing for a therapeutic psychedelic experience.

Over the counter (OTC) analgesics

There are a few different classes of pain relievers that are sold over the counter (OTC) in the United States including acetaminophen/paracetamol (Tylenol), ibuprofen (Motrin, Advil), naproxen (Aleve), and Aspirin. Generally, these medications do not pose any risk of physiological danger in combination with psychedelics, including psychedelics that contain MAOIs such as ayahuasca.

Acetaminophen (Tylenol, paracetamol)

Interestingly, there is an emerging body of research, particularly with acetaminophen (Tylenol) demonstrating that OTC pain relievers can have effects on emotional processing and behavior. It was demonstrated that acetaminophen (Tylenol) has the ability to blunt emotional processing to both positive and negative stimuli. It can also reduce effects of pain secondary to things like social rejection. It appears that it can interfere with our judgement of errors and make us more apathetic to mistakes. The site of interference in error evaluation appears to be in the cortex, which is a site in the brain targeted by psychedelics via their stimulation of 5HT2A receptors. Evidence for an effect on emotional processing is less well established with other OTC analgesics, although ibuprofen has also been shown to have a sex specific effect on emotional processing. How strong these effects on the interference of emotional processing are and whether they could influence psychedelic healing processes in a clinically significant manner is unknown. OTC analgesics have been permitted to be used in protocols of clinical trials utilizing psychedelics to date.

Non-steroidal anti-inflammatory drugs (NSAIDS)

Another more theoretical area of drug interaction involves effect on the immune system and inflammatory responses. Non-steroidal Anti-Inflammatory Drugs (NSAIDS) such as ibuprofen, naproxen (and several other prescription agents such as meloxicam, diclofenac etc.) work by blocking the production of pro-inflammatory mediators termed prostaglandins. Psychedelics are known to have immunomodulatory and anti-inflammatory effects, thus there could be an immune system mediated interaction. The significance of this interaction, if any, is unknown.

Aspirin

Aspirin has a similar mechanism of action to NSAIDS, although low daily doses are often used for advanced cardiovascular conditions. Therefore, when use of low-dose or daily aspirin is reported, a contraindicated condition to psychedelic use may be present.

Due to the benign nature of OTC analgesics from a physical perspective when used with psychedelics and lack of perceptual psychoactive effects, their benefits still likely outweigh risks of interference with emotional processing for minor aches and pains before or after psychedelic experiences. For example, OTC analgesic use prior to psychedelics to relieve menstrual cramps may improve ‘set’ of the user enough to be worth the risk of blunted emotional processing. Similarly, a mild-moderate tension headache is a common side effect the day after psilocybin use and if adequately relieved by an OTC analgesic, it may allow for a less distracted period of reflection in the immediate post-use period, creating a compelling benefit. Conversely, for a new pain or a pain that becomes exacerbated by psychedelic use without an explanatory provocation, it may be preferable to attempt working through pain using psychosomatic processing or other non-drug related methods rather than taking analgesics.

Neuropathic analgesics

Nerve pains are often described as stabbing, shooting, tingling, or burning types of pains and are treated with a variety of analgesics. These analgesics are almost universally active in the CNS and many share therapeutic overlap with other psychiatric or neurologic illnesses including depression, anxiety, and seizure disorders. The only neuropathic agents that are not CNS active involve topical remedies.

Antidepressants

I discuss interactions with antidepressants used for nerve pain such as duloxetine (Cymbalta) and amitriptyline (Elavil) elsewhere. Psychedelics, either in macro or micro doses, may be effective agents in pain conditions. It’s a logical hypothesis to test: if antidepressants work for depression, anxiety nerve pain, or fibromyalgaia and psychedelics also work for depression, anxiety, and have anti-inflammatory effects, that they may have potential to impact nerve pain too.

Gabapentinoids

The gabapentinoids include the agents gabapentin (Neurontin) and pregabalin (Lyrica). They are used for neuropathic pain and anxiety disorders primarily, although gabapentin is also an antiepileptic agent. There is likely some mild interaction potential between gabapentin, pregabalin and psychedelics that may blunt the experience, although user anecdotes don’t support a strong interaction and in a clinical study of MDMA for PTSD, they allowed users to remain on gabapentin when used for pain. There is no rationale to believe that gabapentin or pregabalin would have a high risk of serotonin syndrome or other severe adverse reactions if combined with ayahuasca. Speculatively, they may diminish effects of ibogaine or ketamine due to GABAergic activity.

Both gabapentin and pregabalin have dependence when taken for extended periods of time and can cause withdrawal syndromes if not tapered appropriately. Therefore, in persons with neuropathic pain that are getting a beneficial effect from these agents, it is reasonable to simply continue them. For persons using lower doses for anxiety disorders, tapering the medication over a period of a few weeks may be considered instead.

Opioids

Opioids is an umbrella term that encompasses drugs that produce an analgesic effect by binding with μ-opioid receptors. It includes both naturally derived drugs such as codeine, morphine, and heroin (opiates) as well as synthetics such as oxycodone, methadone, buprenorphine, tramadol, and others. Opioids are notorious for leading to dependence, tolerance, and substance use disorders (addiction) and harms associated with opioids are currently epidemic in the US. They are regulated as controlled substances and produce sedative effects on the CNS, which can lead to fatal respiratory depression in overdose. Drugs that depress CNS activity, tend to generally have blunting effects on psychedelics, although how significant this effect is may depend on individual factors such as tolerance, dose, or the agent(s) used. If an underlying opioid use disorder is present, then the psychedelic ibogaine would likely be of most benefit, although is limited by potential for fatal arrhythmia.

Opioids are oftentimes used for the short-term management of severe pains associated with post-surgical pain, acute physical trauma, or pain flares associated with various medical conditions. For these indications they may be offered ‘as needed’ and taken for such a short period of time or so sparingly that physical dependence does not occur. For the opioid user that doesn’t have a physical dependence on opioids, it is likely best and relatively easy to avoid them for at least 72 hours prior to psychedelic use, which is the timeframe that it could be expected that most opioids used on an as needed basis are eliminated from the body. If persons are experiencing an acute pain flare requiring as needed opioids, it may be best for user set and setting to simply postpone the psychedelic session until the individual is no longer in high amounts of pain and using opioids.

In users of opioids for the treatment of chronic pain in which a substance use disorder is not present, then the choice of psychedelic and management approach is important. Some opioids are contraindicated with ayahuasca or ibogaine. For life-threatening illness or illness in which opioids are medically necessary, continuation of long-acting opioids may be necessary for comfort in user ‘set’.

Which opioids can you combine with ayahuasca?

While opioids all share their activity at μ-opioid receptors, some of them have additional pharmacology at serotonin and norepinephrine reuptake pumps that could introduce serious drug interaction potential with MAOI containing psychedelics such as ayahuasca. The opioids methadone (Dolophine), meperidine (Pethidine), tapentadol (Nucynta), and tramadol (Ultram) and dextromethorphan all have some weak affinity for the serotonin reuptake pump and have been implicated in cases of serotonin syndrome when combined with MAOIs. Therefore, these agents should be either avoided or discontinued at least 5 half-lives ahead of ayahuasca use. The opioids hydrocodone, oxycodone, buprenorphine, morphine, hydromorphone, oxymorphone, heroin and codeine do not have activity at the serotonin reuptake pump and have not been implicated in cases of serotonin syndrome.

Have opioids and psychedelics ever been combined in clinical trials with other psychedelics?

It is relatively common for opioids to be prescribed for pain associated with illnesses such as late stage cancers. In clinical trials of psilocybin assisted psychotherapy for life-threatening illness in which many participants had late stage cancer, the use of long-acting opioid medications (e.g. sustained release morphine or oxycodone) administered every 12 hours were permitted to be used concurrently per the clinical trial protocol. The protocol stipulated that psilocybin administration would be timed 6 hours after the ingestion of their opioid and 6 hours prior to their next dose of opioid. Therefore, it appears their strategy was to time the dose of psychedelic the farthest possible from the previous opioid dose, while still allowing time for the psilocybin experience to unfold prior to the next opioid dose. For serotonergic psychedelics that do not contain an MAOI, such as MDMA, psilocybin, or short-acting inhaled tryptamines (5-MeO-DMT), this strategy would seem to be adaptable. For other serotonergic psychedelics such as LSD or mescaline, the length of the psychedelic effect may present challenges for use of this strategy. Notably, while the trial protocol permitted long-acting opioids, it’s unclear how many trial participants were actually taking them or if their results differed from others in the trial.

How are opioids used with ibogaine?

When ibogaine is used in a person that uses opioids, it is typically with the intention of managing opioid use disorder (OUD) rather than helping mood or having an analgesic effect in a person with chronic pain. Ibogaine is contraindicated to be used in conjunction with long-acting or extended-release formulations as well as the Medication Assisted Treatment (MAT) drugs methadone and buprenorphine. This is because ibogaine is known to sensitize the user to opioids back to pre-opioid use levels, thus opioid use while on ibogaine can be dangerous and increase risks for overdose. Another risk is arrhythmias and cardiotoxicity, which is worsened considerably by methadone. Therefore, ibogaine use should be attempted only in the opioid user that wants to stop using opioids completely and is on a short-acting opioid prior to ibogaine use.

Ketamine

Ketamine is more accurately classified as a dissociative anesthetic rather than a psychedelic. Given anesthetics have sedative properties, there could be additive risks of sedation or respiratory depression when ketamine or opioids are combined. This can become excessively dangerous with high doses, unmonitored environments, or use of other sedatives like GHB, alcohol, or benzodiazepines. Serotonergic psychedelics are likely lower risk psychedelics to use in combination with opioids when it comes to ketamine. Other pain medications such as OTC analgesics possess minimal risk in combination. There may be some theoretical interactions between drugs that interfere with GABA such as the gabapentinoids (gabapentin, pregabalin), although these interactions are not well documented if they are real.

Conclusions

OTC analgesics are low risk with many psychedelics and can be used to help with minor aches and pains that come up around the time of psychedelic use. Prescription agents to manage pain taken on a chronic basis are more complex and should be assessed in the context of user ‘set & setting’ to optimize potential for healing psychedelic experiences. Ketamine has some additional risk with sedative analgesics like opioids, although is combined in clinical practice for opioid-sparing effects. Ayahuasca and ibogaine are special cases in which scrutiny for drug interaction that has physical risks should be assessed, particularly with opioids.

Pain & Psychedelics Part II: Drug Interactions with Analgesics — Spirit Pharmacist

Part II This is the second of two installments in a blog series on pain and psychedelics. In the first installment or Part I I covered mechanisms of psychedelic action in the context of pain, suffering and philosophy. In this installment I cover drug interactions with different classes of analg

www.spiritpharmacist.com

​

 

[mr peabody]

Give cannabis to elderly people with chronic pain, doctors say*

by Tony Diver | The Telegraph | 5 Sep 2020

Experts say cannabis-based medicines, including those that contain THC, should be used instead of opioids.

Elderly people with chronic pain including back and joint injuries should be prescribed cannabis instead of conventional painkillers, doctors have said, as polling shows that three quarters of over-55s would consider taking it.

Doctors said cannabis-based medicines, including those that contain THC, the chemical that makes recreational users high,' should be used instead of opioid medications.

Draft guidance published last month by the National Institute for Health and Care Excellence suggested prescription guidelines for patients with chronic pain will soon move away from drugs like paracetamol, ibuprofen, aspirin and opioid medications such as tramadol, codeine and morphine.

The draft guidance suggests more than a million chronic pain patients in the UK should instead be prescribed group exercise programmes or acupuncture.

But doctors have suggested that patients with back pain could instead benefit from taking cannabis oil, which was legalised for prescription for some conditions in the UK in 2018.

Although cannabis oil is not widely available on the NHS, some private clinics prescribe it if other medication has not worked.

A new poll by Open Cannabis, a campaign to widen access to cannabis medicines in the UK, suggests almost three quarters of people over the age of 55 would consider cannabis medication if it was offered to them, compared to two-thirds of the population as a whole.

The proportion of people over the age 75 with chronic pain in the UK could be as high as 60 per cent, research published by the BMJ suggests.

Use prescriptions to keep patients away from dealers

Dr Steve Hajioff, a former chair of the British Medical Association, said cannabis should be made available legally using prescriptions to prevent patients turning to black market drugs for pain relief.

“Cannabis-derived medicines can help fill the gap in helping people with chronic pain, as we move away from some pain-management procedures and using opioid or non-steroidal anti-inflammatory drugs,” he told The Telegraph.

“Patients who could benefit from cannabis-based medicines need to be made aware of the legal routes to access these treatments in the UK, so that they are not exposed to the dangers associated with the illegal market."

There is no reliable data on how many people in the UK using cannabis illegally for pain relief, but it is thought the number could be in the millions.

Cannabis was legalised for medicinal purposes in the UK in 2018 following a campaign by children with treatment-resistant epilepsy who used oil from the plant to control their seizures.

Patients can now legally be prescribed medicine containing THC, the chemical compound in cannabis that makes recreational users “high” and which is otherwise banned under UK law.

Products that only contain CBD, another chemical in cannabis, are already legal and are widely sold in high street shops.

But despite the law change, few if any prescriptions have been issued on the NHS, after NICE guidelines said doctors should be wary of handing the oil to patients before full medical trials have taken place.

There have been no randomised controlled trials in the UK for medicinal cannabis, and none are expected until at least 2021.

A small study in Canada in 2010 suggested that cannabis could have an impact on long-term pain, which can include back pain and joint pain.

The NHS said a “much larger trial would be needed for a longer period to assess the effects of cannabis properly."

A spokesman for the Open Cannabis campaign said: “Our long term aim is to show the government that medical cannabis is safe and effective and should be available through the NHS for a wider group of people.”

*From the article here :

Give cannabis to elderly people with chronic pain, doctors say

Experts say cannabis-based medicines, including those that contain THC, should be used instead of opioids

www.telegraph.co.uk

 

[mr peabody]

Wearable ketamine delivery device an alternative to opioid-based pain management*

by Sam Woolfe | LUCID News | 29 Oct 2020

Recent research suggests that low doses of psychedelic compounds such as LSD and ketamine can help alleviate pain. Could therapies that use small amounts of these substances be the future of pain management?

Bexson Biomedical believes that its system for delivering low doses of ketamine may provide an effective alternative to opioid-based pain relief strategies which have greater potential for addiction. The company has teamed up with the device manufacturer Stevanato Group to create a wearable ketamine delivery device for patients who need short term relief from chronic and acute pain after receiving surgery. The device and its proposed ketamine therapy are still in the early stage of research.

“Post-operative pain is one of the leading drivers in the opioid crisis. If you want to move the needle on opioid addiction in America you need to provide a new, non-opioid therapy that patients can go home with that has opioid-level efficacy,” Gregg Peterson, Chief Executive Officer at Bexson, told Forbes. “We think our product will be able to do that.”

According to Bexson, doctors are already providing ketamine for postoperative pain relief through intravenous infusions at clinics or hospitals that allow for “steady state plasma levels” or a consistent level of effective pain relief. Megan Oxley, an emergency physician and vice president of the American Society of Ketamine Physicians, says that "for relief from the type of acute pain that a person would experience after breaking a leg or recovering from surgery steady state [plasma] levels probably do allow for better pain control.”

Patients who are discharged from the hospital are not typically offered ketamine infusions by medical providers. While some people use ketamine lozenges for pain relief, patients are instead often prescribed opioids.

Oxley says Ketamine infusions also aren’t offered for home because this form of administration needs to be monitored. “Chronic pain can certainly be treated with other forms of ketamine at home. It is harder to treat acute pain with the current home options but it can be done,” says Oxley.

The new technology now being developed by Bexson is a customized modification of Stevanato’s patented SG EZ-be Pod portable insulin delivery device. It includes a disposable pod containing between 20 and 70 milligrams of ketamine, a needle, and a Bluetooth-enabled control unit that slowly delivers the dose over a period of 24 hours. According to Bexson, the pod has anti-tampering technologies that prevent the user from increasing the intended dosage, whether by mistake or deliberately. Bexson did not provide detailed information about how these anti-tampering systems are expected to operate.

The Bexson device delivers ketamine subcutaneously, which means it enters the layer of fat between the skin and the muscle. To increase the bioavailability of ketamine through this method, Bexson is developing a proprietary formulation of ketamine, BB106, with a higher pH. Company co-founder Jeffrey Becker, who is a psychiatrist, emphasizes that "the system provides a low dose of ketamine, rather than a microdose," adding that "the company is not currently developing a `microdose’ use case.”

Bexson says it is targeting the $12 billion dollar market for post-operative pain control. The company will start animal testing on its ketamine delivery product this year and plans to launch a phase one clinical trial in 2021. It has not yet released peer reviewed research demonstrating the effectiveness of its BB106 formulation.

Medical researchers are raising questions about potential damage to the epithelial lining of the bladder caused by sustained ketamine use in different kinds of therapies and usage patterns. Researchers have not flagged any specific concerns about the Bexson device.

Bexson believes that its device could gain FDA approval by 2026. In the meantime, the company says it is devising ketamine formulations to target other conditions, including mental health treatments. Based on its present research plan, Bexson is in the process of closing a Series A funding round, its first significant round of venture capital funding.

Propriety formulations and patented delivery systems can sometimes increase the cost of ketamine-based therapies. Spravato, the prescription esketamine nasal spray developed by the Janssen Pharmaceuticals unit of Johnson & Johnson for treatment resistant depression (TRD) and major depressive disorder (MDD), is administered in 28 mg, 56 mg, or 84 mg doses. A full 84 mg dose can cost $850 with an induction regimen that includes two treatments a week for three weeks. This does not include the cost of two hours of supervision which are required by the FDA and the manufacturer.

According to a Bexson spokesperson, the company has not yet identified a price point for their ketamine delivery device for pain relief. As it is not a mental health treatment, patient care is expected to follow a different model. According to a statement by Steven Kaufman, Vice-President of Drug Delivery Systems for the Stevanato Group, the modified SG EZ-be Pod device will help keep treatment costs down. “This design will support patient comfort with a discreet and intuitive device, and by utilizing our patented technologies, we address the importance of sustainability, while minimizing the overall cost per treatment,” said Kaufman.

“I believe, this is my opinion, because you are using the cheaper generic version of ketamine, the administration system is the expensive and patented part,” says Oxley, the physician. “But you can price it however you want and make sure you are lower than your competition. Remember Spravato is a patented medication, Bexson created a delivery device, but is using a generic old medication.”

Ketamine was first used as a veterinary anesthetic in 1963. Research strongly suggests that ketamine can also be a fast-acting and highly effective antidepressant. Patented for human use in 1966 and approved four years later by the FDA, ketamine has a long history of use as an anesthetic beginning with the treatment of soldiers during the Vietnam War. Together with a team of investigators, Dr. Carlos Zarate, a psychiatrist working at the National Institute of Mental Health (NIMH) published in 2006 seminal research on the use of IV ketamine as a therapy for treatment-resistant depression.

Medical professionals like Oxley offer ketamine off-label for mental health treatments as intramuscular injections, IV treatment or via lozenges. The National Institute of Mental Health (NIMH) investigated ketamine for the treatment of depression. The Yale University School of Medicine developed what is known as the NIMH protocol which uses .05 mg/kg per 40 minutes IV dosage for treatment-resistant depression which is typically repeated over the course of six treatments in two or three weeks.

Becker, who serves as Chief Scientific Officer at Bexson, says that "when Bexson’s ketamine delivery device is tailored for mental health conditions instead of pain relief, the doses may be higher as is clinically appropriate.” Specific doses will be fine-tuned based on data from Phase I and II studies.

Peterson told Forbes that "the ketamine dosage delivered by the Bexson device for pain relief will result in a mild altered state similar to ingesting a glass of wine, maybe a martini.” But according to Bexson, "the device will support dosage control and reduce the need for patient monitoring."

Becker asserts that “ketamine is not as easy to abuse [as opioids]” and notes that "the device’s delivery method only makes low doses available to patients, which is key to the device’s safety."

While prescription opioid painkillers are one of the most common treatments for postoperative pain, these medications are a major factor in the opioid crisis in the U.S., which sees increasing numbers of people succumbing to opioid addiction and sometimes fatal overdose. Peterson told Lucid News that by “providing an effective non-opioid therapy for at home use, we believe we can reduce opioid addiction rates, and ultimately opioid-related overdose deaths.”

Elias Dakwar, an associate professor of Clinical Psychiatry at Columbia University, agrees that this delivery method reduces the chances for the type of addiction patterns that patients encounter with opioids.

“Low dose infusions of ketamine have a very low potential for being abused given reduced psychoactive effects. They have been used in pain management settings for many years in inpatient settings, without incidence of abuse,” says Dakwar. “It is likely that their use in outpatient settings through a device will be similarly safe.”

Given that the anticipated dose of ketamine for Bexson’s device may still produce mild psychoactive effects, Dakwar recommends that users avoid operating any heavy machinery and driving when the infusion itself is taking place. "Low dose infusions of ketamine," says Dakwar, “are known to address chronic pain, acute pain, and refractory pain; they may also reduce the need for opioids, without necessarily replacing them altogether.”

Wearable Ketamine Delivery Device Developed As Alternative to Opioid-Based Pain Management - Lucid News

Therapies using small amounts of psychedelic compounds may be the future of pain management.

www.lucid.news

 

[mr peabody]

Ketamine for Pain – The Pros and Cons*

by Karla Ilicic | Healing Maps | 25 Aug 2021

Ketamine treatments continue to gain popularity to help treat anxiety, PTSD, and depression. But using ketamine for pain is also beginning to show positive results.

The reasoning behind using ketamine for pain stems from its use in the medical field. There, it’s well-known as a strong and efficient analgesic, a complementary drug in perioperative setting, as well as an accessory drug for opioid-resistant pain in palliative care and for intractable chronic noncancer pain.

Studies on using ketamine for cancer treatment is limited. That said, there’s plenty of research that supports its effectiveness in decreasing pain levels after surgery, as well as reducing opioid requirements. One study even found how ketamine has remarkable analgesic benefits for serious surgeries. This supports other available research showing how ketamine is most effective when pain levels are high or chronic.

When it comes to chronic pain, ketamine treats syndromes with a neuropathic element as a low dose of this psychedelic seems to reduce inflammation at the most crucial sites.

What actually is pain?

Before delving deeper into understanding how ketamine for pain relief is an option, here’s a breakdown of pain itself.

Pain is literally a signal your nervous system receives that tells him something may be wrong. It shows up as a very uncomfortable and unpleasant feeling in the form of a burn, sting, ache, prick, or a tingle. That feeling may come or go, and it can be located at a specific area of your body, a larger region, or even all over.

When it comes to types of pain, there are two: acute and chronic. Acute pain is sudden, usually a direct consequence of an injury, disease, or inflammation. When treated on time, it goes away. If not treated on time, acute pain can turn into chronic pain. Chronic pain is ongoing and lasts for longer than six months, as pain signals in the nervous system remain active even after the initial cause goes away.

How to handle different types of pain

Chronic pain is harder to treat, as it can persist for months, even years. This causes prolonged periods of inflammation and stress to the body, which can yield long-term consequences. Some of these might be physical — like nerve overstimulation, tense muscles, lack of energy, limited mobility, gastrointestinal issues. However, others may be psychological and emotional, like anxiety, fear, depression, and mood swings.

Pain also isn’t always curable, but it’s treatable. In many cases, it’s possible to keep it under control when consistent in using available resources. Things like pain relievers, therapeutic treatments, acupuncture and acupressure, holistic practices, and psychedelics like ketamine can help alleviate pain.

Still, pain is important as it’s a clear sign of something not functioning right in the body. Sometimes, the cause is known (an immediate injury, known illness, or inflammation). However, other times it’s unknown, and it’s important to investigate further to find the root cause as pain.

Ketamine infusions

As ketamine treatments are becoming more and more popular, the term “ketamine infusions” is leaving many people still uncertain of how they work.

Ketamine infusions are one of two possible ketamine treatment options available at ketamine clinic worldwide. Each treatment usually lasts around 40 minutes and it’s under the strict supervision of the doctor who administers it.

Already known as an efficient treatment against anxiety and depression, ketamine offers patients more than mental health relief. From helping control eating disorders and substance abuse, to stress management and relieving chronic pain.

Pros of using ketamine for pain

Ketamine administration can be useful when it comes to dealing with pain, and here are some main reasons.

Non-drug option

One of the advantages of using ketamine for pain relief is that it’s not a typical medical drug. As a psychedelic and analgesic, it provides help by binding to the NDMA receptors in the brain, which control the strengthening and weakening of the synapses, as well as play an important role in memory and learning.

When ketamine binds to the NDMA receptors, it blocks them. In turn, this increases glutamate, an important amino acid present in almost 90 percent of all brain synapses. This part of the brain is responsible for thousands of functions. This binding is the reason for ketamine’s psychedelic effects on the body — which can cause hallucinations, visual and auditory distortions, disorientation, confusion. However, this is also responsible for relieving and reducing pain levels.

Anxiety and stress-reducing

Pain is mostly a physical sensation, but it may strongly affect a person’s mental state as well. Fear of pain and fear of re-experiencing pain is a struggle most people have. This is common even after the initial injury or illness has gone away or has healed.

Since ketamine’s introduction into the psychedelic world, it’s mostly been tool to help deal with anxiety and stress. Consequently, ketamine could help deal with the fear and anxiety caused by experiencing pain. This is especially true in chronic cases, where issues can drag on for months or years.

Fast-acting symptom relief

Ketamine is a powerful anesthetic specifically because of its fast-acting characteristic, causing the symptoms to subside much sooner than any other type of analgesic. This feeling is what helps in relation to pain relief.

Cons of using ketamine for pain

Now that we’ve explored the pros, it’s time to go over the potential cons of using ketamine for pain. These include the following.

Addictive potential

Although there’s evidence that shows ketamine can be useful in the treatment of substance abuse, this psychedelic has the potential of developing addiction. And when it comes to relieving pain, it wouldn’t be the first painkilling drug with the risk of addiction.

Since the potential of becoming addicted to ketamine exists, it shouldn’t be underestimated. Similar to other negative addictions, this could cause further issues in multiple areas of their life.

Lack of regulation and legal questions

Despite an abundance of ketamine clinics, the FDA has yet to approve or regulate ketamine infusions as a treatment option. Although not illegal, there’s still a risk of getting the wrong dosage.

This is what the American Society of Anesthesiologists, the American Society of Regional Anesthesia and Pain Medicine, and American Academy of Pain Medicine tried to tackle by issuing guidelines in 2018 for the use of intravenous ketamine for chronic pain. These are mandatory for all American anesthesiologists administering ketamine for a chronic pain indication.

Unfortunately, despite the aforementioned guidelines, there remain to be issues. Most of these stem from inadequate guidance surrounding optimal dosing and potential risks of with treatment.

Lack of research when using ketamine for pain

As with all psychedelics, one of the biggest cons still presents the lack of available research. Despite numerous studies ongoing over the past decade, many are still all in their infancy. Large scale studies are ongoing to explore how the brain reacts to psychedelics. Additionally, research is necessary to understand how ketamine can help alleviate mental and physical issues.

As psychedelics continue gaining trust from medical professionals, steps towards legalization progresses. We’re not there yet, but we do keep getting better insight into the healing potential each day.

*From the article here :

Ketamine For Pain: Understanding The Pros And Cons

As more people turn to ketamine for pain relief, this explains the benefits, addresses the issues, and helps answer additional questions.

healingmaps.com

 

[mr peabody]

Low-dose LSD significantly reduces pain perception*

by Abigail Calder, MSc | Psychedelic Science Review | 8 Oct 2020

A new clinical study reports that 20µg of LSD significantly reduces pain perception. This promising investigation builds on the little-known history of research into LSD as a potential analgesic.

In the 1960s, Dr. Eric Kast had a theory of pain. More than just a physical response to damage, he knew that pain has essential psychological components. It demands attention, sometimes obscuring everything else. And Kast observed that patients in pain suffer from contradictory desires: They want both to maintain their bodily integrity and to separate themselves from the parts of the body that hurt.

Dissatisfied with the standard opioid pain treatments, Kast went on a quest to find an “ideal analgesic.” Enter LSD: Because it disrupts processes of attention, Kast hoped that the then-novel psychedelic could loosen the death-grip that pain holds on a patient’s mind. And he wondered whether LSD’s ability to obliterate ego boundaries would allow patients to separate themselves from their pain in a way that would not normally be possible.

Kast’s experiments were both successful and disappointing. For patients with extreme pain, a full hallucinatory dose of LSD was a more effective analgesic than opioids. Some patients even temporarily developed a more carefree attitude towards their illnesses. But because the psychedelic experience was so mentally taxing, many of the dozens of patients Kast treated were not eager to undergo it again. After three weeks, their pain levels returned to baseline, and research on LSD came to a decades-long halt soon after.

Less is more

Hallucinogenic doses of LSD may be effective against pain, but they are also – to understate things – impractical. Yet until recently, scientists had never tried lowering the dose. Small doses of LSD, also called microdoses, do not cause hallucinations but may preserve some of the drug’s other effects. This was the driving idea behind a new study from Ramaekers et al., which investigated LSD’s analgesic properties in healthy people.

Using the gold standard randomized, double-blind design, researchers invited twenty-four participants to receive up to 20µg of LSD – or a placebo – on four different occasions. At 1.5 and 5.0 hours after each person took LSD, researchers had them immerse a hand in ice-cold water until they “can't take it anymore.” This was their strategy for measuring pain perception, and the researchers hypothesized that participants would be able to keep their hands submerged for longer after taking LSD.

At a dose of 20µg, that is precisely what happened (the lower doses of 5 and 10µg had no effect). When participants received 20µg of LSD, they endured the cold water for 20% longer, and they also felt that the sensation was less painful and unpleasant. This finding was not only impressive for its own sake but also because it is comparable to the effects of moderate to high doses of opioid painkillers on the same cold water test. The authors theorize that the effect could hold for up to twelve hours.

Notable – and perhaps concerning – is the fact that pain relief was not the sole effect of the 20µg dose. On average, it also made participants slightly more anxious, and it mildly increased physical discomforts like dizziness and nausea. Additionally, it increased feelings of dissociation, which the authors theorized could contribute to pain relief (Eric Kast would approve). Current pain medications have their trade-offs, and LSD may be no different, although some would argue that it has a favorable profile compared to opioids.

The many facets of pain and LSD

The idea that a hallucinogen could reduce pain perception may seem to come out of nowhere. But LSD has several properties that may explain this surprising find. The first goes all the way back to Eric Kast: LSD might make it easier for people to mentally separate themselves from their pain. People may begin to interpret it differently and lose the strong emotional reaction to it that characterizes suffering in chronic pain.

Just as pain is many-faceted, so may be LSD’s analgesic mechanisms. Psychedelics moderately raise blood pressure, which may inhibit particular pain pathways. The effect is small, but present: Ramaekers et al. saw that the LSD-induced increase in blood pressure explained 14% of the variance in pain perception.

Moving on down the list of potential analgesic mechanisms, LSD’s activity at serotonin receptors – especially 5-HT2A – may inhibit certain pain processing pathways, while also elevating mood. It seems to “close the pain gate”,” although exactly how this works is not well understood. Additionally, most psychedelics seem to have anti-inflammatory properties, probably through the unique way they bind to certain serotonin receptors. Inflammation is a well-known cause of chronic pain: the normal response to tissue damage can become dysregulated and cause conditions like rheumatoid arthritis and other autoimmune disorders.

And LSD’s potential as an analgesic also comes from the properties it does not have. Unlike opioids, it is not known for causing drowsiness or slowed breathing, and deadly overdoses are nearly unheard of. Perhaps most saliently, it does not cause addiction or a withdrawal syndrome. Hopes for an “ideal analgesic” may be disappointed, but LSD could be more manageable, at least for some patients, than opioids.

Conclusion

It’s no secret that LSD is capable of a varied collection of effects. A small, non-hallucinogenic dose dampened pain perception in healthy volunteers, possibly adding analgesia to that long list.

But having explained how cool and promising these findings are, it is time for a parting spritz of rain on the parade. Pain is highly contextual, and the participants’ experiences in this study are quite unlike the experiences of patients with chronic conditions. Study participants can end their discomfort at any time, and they know it will end. Those with chronic pain conditions have inescapable, enduring, and often more severe pain, with varying causes. That LSD dulled pain perception in healthy volunteers is promising, but future research with patients will have the last word. Plans for such studies are surely afoot.

*From the article here :

Low-Dose LSD Reduces Pain Perception

A new clinical study reports that 20µg of LSD significantly reduces pain perception. This promising investigation builds on the little-known history of research into LSD as a potential analgesic.

psychedelicreview.com

 

[mr peabody]

Study: Nearly half of medical cannabis users cease using opioids for pain after twelve months

by NORML | 21 Jan 2021

Patients authorized to use medical cannabis significantly reduce or eliminate their use of opioids over time, according to longitudinal data published in the Canadian Journal of Anaesthesia.

A team of Canadian investigators assessed self-reported opioid consumption patterns over time in a cohort of authorized medical cannabis patients who suffered from pain-related issues. Consistent with numerous other studies, researchers reported that many subjects tapered their use of opioids following medical cannabis initiation.

“The proportion of individuals who reported using opioids decreased by half over a period of twelve months," they determined.

In addition, subjects’ “pain intensity and pain-related interference scores were reduced and [their] quality of life and general health symptom scores were improved compared with baseline.” Authors also noted that many subjects switched from consuming herbal cannabis to ingesting oil extracts over the course of the trial.

Authors concluded: “Over time, individuals who continued consuming cannabis within this longitudinal study reported lower pain severity and pain interference scores, as well as improved quality of life and general health symptoms scores. … Beneficial effects of cannabis appear to persist long-term and tolerance may not become a significant issue for patients on a stable regimen. … The proportion of patients using opioids at each follow-up was decreased, … suggesting an opioid-sparing effect with cannabis use. … Our data speaks to the need for robust clinical trials, given the overall increase in opioid cessation for those that remained on cannabis.”

The study comes only weeks after separate longitudinal data, also from Canada, reported that patients prescribed opioids reduce their mean opioid dosage by over 70 percent following the use of medical cannabis.

Commenting on the findings, NORML’s Deputy Director Paul Armentano said: “The data to date is consistent and persuasive: For many pain patients, cannabis offers a viable alternative to opioids, potentially improving their quality of life while possessing a superior safety profile.”

Full text of the study, “Patient-reported outcomes in those consuming medical cannabis: A prospective longitudinal observational study in chronic pain patients,” appears in the Canadian Journal of Anaesthesia. Additional information is available in the NORML fact-sheet, “Relationship Between Marijuana and Opioids.”

Study: Nearly Half of Medical Cannabis Users Cease Using Opioids for Pain After Twelve Months - NORML

“Over time, individuals who continued consuming cannabis within this longitudinal study reported lower pain severity and pain interference scores, as well as improved quality of life and general health symptoms scores."

norml.org

​

 

[mr peabody]

Study finds arthritis patients benefit from medical cannabis and CBD*

by Steven Bridge | CBD Testers

Medical cannabis and CBD have proven over the years that they can help people suffering from arthritis. A new study claims that 90 percent of patients who tried cannabis felt relief from their symptoms.

The survey was carried out by CreakyJoints, a nonprofit under the Global Healthy Living Foundation. CreakyJoints offers support to people living with arthritis and wanted to look at the efficacy of medical cannabis and CBD for treating the disorder. It’s been suggested for years that cannabis and CBD contain analgesic and anti-inflammatory properties. Many chronic pain sufferers around the world also choose cannabis over prescription medication in many cases.

The FDA is scrambling to get a hold on cannabis and CBD, as it becomes legal across many states in the US. Due to various reasons, cannabis is unregulated on the whole, and the CBD industry is even more problematic. At the same time, the Transportation Security Administration recently announced a new policy that allows medical cannabis patients to fly domestically and internationally with their medication.

One thing is abundantly clear; more research and clinical trials are needed to understand the profound effects medical cannabis and CBD can have for a range of conditions. These include things like chronic pain, but also conditions like anxiety and insomnia. That’s the main reason for the CreakyJoints study, as they wanted to understand how members of their community use cannabis for their symptoms.

The findings were presented at the 2019 Annual European Congress of Rheumatology conference in Madrid. A total of 1,059 arthritis patients filled out a questionnaire containing 77 questions, to better understand medical cannabis and CBD usage for arthritis. At least 57 percent of the participants said they’ve tried medical cannabis or CBD (or both) to help with their pain. The majority of patients surveyed either had rheumatoid arthritis or osteoarthritis, while a smaller percentage suffered from psoriatic arthritis, fibromyalgia, and ankylosing spondylitis.

Participants also commented that they didn’t only use medical cannabis and CBD for pain but also a range of other issues related to their condition. These included things like insomnia, depression from pain, nausea, physical function, and fatigue. The amazing statistic to come out of the study was that 97 percent of people living with arthritis said that cannabis had helped to ease their symptoms. At the same time, 93 percent reported that CBD was the compound they preferred that was effective for them.

Another interesting thing to come from the survey was the issue of doctor-patient conversations when it comes to cannabis and CBD. Around 45 percent of participants said they started taking either cannabis or CBD or both to treat their arthritis symptoms despite being on prescription medication already.

W. Benjamin Nowell, Ph.D., Director of Patient-Centered Research at CreakyJoints said, “Anecdotally, and via this survey data, we know that there are many people with arthritis who benefit from marijuana and CBD products. However, we have to temper our potential excitement about adding these products to an arthritis management strategy because there is so much yet to learn about how these supplements interact with people’s prescribed and over-the-counter medicines and if, in fact, they can be proven to positively impact a person’s experience of disease and symptoms.”

Nowell also noted that “It’s vital that marijuana and CBD products are tested for their safety, dosing, and effectiveness in randomized controlled trials, which are the gold standard for understanding the risks and benefits of treating disease.” That’s why many people across different industries are pushing for more studies on cannabis and CBD to see if they could be a solid, long-term solution for arthritis patients.

*From the article here :

New Study Finds Arthritis Patients Benefit From Medical Cannabis and CBD - CBD Testers

A new study claims that 90 percent of patients who tried cannabis or CBD felt relief from their arthritis-related symptoms.

cbdtesters.co

 

[mr peabody]

Cannabis mitigates symptoms in patients with Fibromyalgia*

by NORML | 19 Feb 2021

The adjunctive use of cannabis is associated with improvements in pain and other symptoms in patients with refractory fibromyalgia, according to data published in the Journal of Cannabis Research.

An Italian researcher assessed the long-term use of various types of cannabis preparations (e.g., herbal cannabis, oil extracts, etc.) in a cohort of 38 patients with treatment-resistant fibromyalgia. Participants in the study consumed cannabis for up to twelve months in combination with their prescribed medications.

The author reported that “significant improvements were observed” following the initiation of cannabis therapy in most patients. Participants were most likely to report reductions in pain, as well as declines in their disability index and overall symptom severity scores. Most subjects who were responsive to medical cannabis reported experiencing “no or mild side effects.” Subjects also did not appear to develop long-term tolerance to the substance, as patients had no need to increase their dosages of medical cannabis over the duration of the study period. No improvements in patients’ anxiety or depression scores were reported.

Similar to the findings of other studies, the majority of trial subjects who responded favorably to cannabis therapy either discontinued or significantly reduced their consumption of prescription medicines.

The study’s author concluded: “The current study revealed the positive effects of MC [medical cannabis] therapy in some patients with FMS [fibromyalgia syndrome] and resistance to conventional treatment. Thus, cannabinoids may be considered for FMS treatment, although several side effects may still occur. Further studies are warranted to confirm these findings.”

Numerous studies of fibromyalgia patients – such as those here, here, here, and here – have also concluded that cannabis is effective and well-tolerated in patients with FMS.

NORML’s Deputy Director Paul Armentano said: “A growing number of patients with fibromyalgia are experimenting with cannabis products. This study’s findings add to the growing body of literature indicating that cannabis is a promising alternative therapeutic option for many of these patients.”

Full text of the study, “Medical cannabis for the treatment of fibromyalgia syndrome: A retrospective, open-label case series,” appears in the Journal of Cannabis Research. Additional information on cannabis and fibromyalgia is available from NORML here.

*From the article here :

Study: Cannabis Mitigates Symptoms in Patients with Treatment-Resistant Fibromyalgia - NORML

“The current study revealed the positive effects of MC [medical cannabis] therapy in some patients with FMS [ fibromyalgia syndrome] and resistance to conventional treatment. Thus, cannabinoids may be considered for FMS treatment."

norml.org

​

 

[mr peabody]

Naltrexone promising for treatment-resistant chronic pain*

by Fran Lowry | Medscape | 30 Apr 2021

Low-dose naltrexone (LDN) may be effective in the treatment of refractory chronic pain, early research suggests.

Preliminary data from a retrospective chart review of patients with chronic pain showed those who received LDN experienced significant improvement in both pain and disability.

"Naltrexone has been studied especially in the setting of opioid and alcohol abuse, but we're seeing that at low doses, it has a paradoxical effect where it exhibits anti-inflammatory properties and it may be beneficial for patients with fibromyalgia or low-back pain," study investigator Kaivalya Deshpande, MD, a resident at the University of Pittsburgh Medical Center (UPMC), told Medscape Medical News.

"The results showed that with appropriate patient selection, LDN could be an additional treatment option within the pain physician's tool kit," Deshpande said.

In addition, because the dose of naltrexone used to treat pain is so low at just one tenth of the actual dose used in addiction, the potential for addiction is low, he noted.

"With high-dose naltrexone, you definitely have some of those risks of addiction, but thus far, there hasn't been any documented abuse potential with low-dose naltrexone," he added.

The findings were presented at the virtual American Academy of Pain Medicine (AAPM) 2021 Annual Meeting.

Refractory patients

The investigators wanted to understand the effects of low-dose naltrexone as an adjunctive treatment in their chronic pain patients, many of whom are resistant to first-line treatments.

The study included 65 patients attending the UPMC pain clinic. All had experienced pain for more than 3 months from either low-back pain with radiculopathy or fibromyalgia. They also had failed traditional treatment strategies including physical therapy, anti-inflammatory and neuropathic pain medications, and epidural steroid injections.

All patients filled out standardized pain inventories to measure pain, disability, and the impact of naltrexone on their ability to carry out daily activities. Deshpande noted these surveys are helpful in tracking patient progress.

"Pain is such a subjective modality so it's really important to evaluate outcomes, especially function, to be able to say a particular intervention has been effective," he said.

"While there are many variables unable to be controlled for within a retrospective study, we were able to follow longitudinal outcomes of patients on low-dose naltrexone to assess if the medication was contributing to some of the benefit that we were seeing," he added.

Patients received low-dose naltrexone for a minimum period of 1 month and were followed longitudinally.

Outcome measures included pain scores, percent improvement in disability, the Oswestry Disability Index (ODI), the Pain Catastrophizing Scale, and Patient-Reported Outcomes Measurement Information System (PROMIS) metrics.

Viable treatment option?

Preliminary data analysis showed a statistically significant improvement in pain scores, percent improvement in disability, and ODI scores for patients who received low-dose naltrexone. These improvements were found at 3 and 6 months after treatment initiation.

Patients also reported improved sleep and decreased pain interference using the PROMIS metric. Numerical Pain Scale scores improved from an average of 8 to 5 at 3 months following the start of low-dose naltrexone.

In addition, investigators found a 40% improvement in disability at 3 months, and this improvement increased to 50% at 12 months. ODI scores improved from 50 to 44 at 3 months after treatment initiation.

"Adverse events included dry mouth, headache, dizziness, gastrointestinal upset, and vivid dreams. However, these were transient and generally mild," Deshpande said.

"Overall, we definitely saw positive results in our clinic with low-dose naltrexone with the pain and disability scores," he noted.

Deshpande reported that the investigators' next step is to review other metrics to examine potential improvement in psychosocial or fitness outcomes.

"Ultimately, it will be important to do a randomized control trial to eliminate potential confounding variables and increase the study's generalizability, in order to be able to say that LDN is helpful. But we can use this study as a foundation for such a trial," he said.

"I definitely think this is promising data that can be used to guide further studies," Deshpande said. "For now, we can say that low-dose naltrexone has potential. It has a fascinating mechanism of action, safe side-effect profile, and for the right patient it can be a viable treatment option."

Critical preliminary data

Commenting on the findings for Medscape Medical News, W. Michael Hooten, MD, professor of anesthesiology at Mayo Clinic, Rochester, Minnesota, noted that "naltrexone is generally considered not to have any abuse potential."

Hooten, who is also president-elect of the AAPM, was not involved with the current research. He added that the results may help expand the potential number of patients who could be candidates for low-dose naltrexone therapy.

"It provides the critical preliminary data necessary to conduct a prospective randomized placebo-controlled trial," Hooten said.

*From the article here :

Addiction Medication Promising for Chronic, Refractory Pain

Used primarily for addiction, low-dose naltrexone may also turn out to be a useful treatment for refractory chronic pain, early research suggests.

www.medscape.com