• Psychedelic Medicine

CHRONIC PAIN | +80 articles

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Lower dose ketamine just as effective as standard dose for treating pain in adults

Loyola University Health System | News Medical Life Sciences | 10 Mar 2021

A recent Loyola Medicine study found that reducing the standard dose of IV-administered ketamine in half is as effective as the larger, standard dose in reducing pain in adults.

Ketamine is known to provide pain relief comparable to opioid medications, which are highly addictive. In the recent study, appearing in the journal Academic Emergency Medicine, researchers studied 98 patients, ages 18 to 59, who presented to the emergency department with acute, moderate to severe pain.

The patients were randomized prospectively to receive either 0.15 mg/kg of ketamine (low dose) or 0.30 mg/kg (high dose). Patients and providers were blinded to dose, with the primary outcome of pain measured on the 11-point numerical rating scale (NRS) at 30 minutes. At 15 minutes, the high dose group had a greater decrease in pain on the NRS but more adverse events. At 30 minutes, adverse events and pain were similar.

Overall, patients generally reported that they would take ketamine again for pain - 76% in the low-dose group and 62% in the high-dose group.

The study did not find a significant reduction in side effects from the lower dose.

"As we continue with our research, we hope to find data that supports diminished side effects with the lower dose of ketamine with equal efficacy in treating pain," said senior study author Megan A. Rech, emergency medicine clinical pharmacist at LUMC and an adjunct assistant professor and research coordinator at Stritch.

*From the article here :
 
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Cannabis found to mitigate 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 :
 
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Medication



Psychedelic medicines for pain go mainstream*

by Frieda Wiley, PharmD | Drug Topics | 16 Jul 2020

An estimated 32 million individuals 12 years and older used psychedelic medicine in the United States in 2010, according to a US population survey. As the opioid epidemic has eclipsed concerns about illegal drugs in recent years, the medical community and the federal government alike have begun reexamining certain illicit drugs as potential alternatives to opiates in pain management.​

Cannabis

Cannabis has been studied extensively for its potential benefits in neuropathic pain, chronic pain, and inflammation. A 2014 study found that most patients cited relief from chronic pain as the most common reason for their medicinal use of cannabis. Yet the plant's psychoactive properties continue to draw concerns regarding abuse potential, owing to the effects of 1 phytochemical, Delta-9-tetrahydrocannabinol, known for its psychoactive properties.

However, these are not the only challenges pharmacists face when it comes to assisting patients. "The biggest pitfall in advising patients on cannabis is that dosing is so difficult to standardize," said Victoria Starr, RPh, a cannabis pharmacist at SageLife, LLC, in Portland, Oregon.

Cannabis for medicinal purposes is highly complex, largely because of its high number of phytochemicals, called constituents. To date, the plant has been found to contain more than 560 constituents. When individuals consume these as the whole plant, the chemicals offer synergistic and therapeutic benefits while mitigating potential toxicities, what's known as the entourage effect. Synthetic cannabis typically contains only 1 active ingredient and lacks additional chemicals that can help regulate undesirable effects. However, customizing cannabis dosing to even the individual patient is no small feat.

"Besides attaching medical benefits to each of these components, the combination of synergistic benefits needs to be determined, along with the proper ratio and dose," Starr explained. "So unlike Western medicine, in cannabis, there exists a multitude of different medications—with a wide range of potencies, targeting a vast array of medical conditions—made up of varied combinations of cannabinoids, terpenes, and flavonoids."​

Psilocybin

Psilocybin, the primary ingredient found in mushrooms that produce psychoactive effects, in enjoying an increased share of popularity and renewed exploratory use.

"It’s exciting that patients are starting to ask their pharmacist about psilocybin,” said Emily Kulpa, PharmD, an integrative health pharmacist and psychedelic medicine consultant based in Milwaukee, Wisconsin.

Although psychedelic mushrooms have been used for millennia, they gained popularity in the United States for recreational use during the 1960s and had spawned some academic interests as well. From 1960 to 1962, psilocybin, along with psychedelic relatives lysergic acid diethylamide (LSD) and mescaline, became the focus of a series of trials known as the Harvard Psilocybin Project. At the time, these drugs were legal. Criminalization of these drugs would later erupt in the following decade as safety concerns grew.

Fast-forward to the new millennium. Psilocybin sparked some interest in its potential analgesic effects in cluster headaches and migraines. Psilocybin agonizes the 5-hydroxytryptamine receptor and may interact with nociceptive and antinociceptive processing. The results from one 2016 retrospective study Googling the keywords “cluster headache discussion forums” and “migraine discussion forums” found that patients who self-treated themselves with psychedelic tryptamines such as psilocybin and LSD reportedly experienced a reduction in cluster frequency and severity.

Although these claims may warrant clinical study in pain management, research has focused on the role of psilocybin in mood disorders. Kulpa credits events in popular culturwith helping bring psilocybin into the mainstream. In the fall of 2019, Johns Hopkins announced the opening of the Center for Psychedelic & Consciousness Research, the first institution in the United States devoted exclusively to psychedelic research.​

Kratom

Indigenous to Thailand, Malaysia, Myanmar, and other regions of Southeast Asia, kratom (Mitragyna speciosa) belongs to the coffee family and also exhibits dose-dependent sedative and stimulatory effects. The plant is typically consumed in pill, capsular, or extract form, although some individuals brew dried or powdered leaves as a tea. Others may chew, smoke, or consume the leaves in food. However, because of kratom’s harmful adverse effects and abuse potential, the FDA warns individuals against using the substance.

Kratom contains mitragynine, an alkaloid bearing a tryptamine-like structure that exhibits µ- and ∂-opioid receptor agonist activity that results in dose-dependent stimulatory and analgesic effects. In lower doses, mitragynine produces stimulatory effects, whereas higher doses result in opioid-like activity. However, its metabolite, 7-α-hydroxymitragynine, exhibits significantly stronger µ-opioid receptor agonist behavior.

Although kratom is not an opioid, the CDC found an association between kratom use and overdose deaths, also involving opioid and nonopioid use, in the State Unintentional Drug Overdose Reporting System. Moreover, based on toxicology results, medical examiners or coroners determined kratom as the culprit in deaths in 11 states from July 2016 to June 2017 and 27 states during the last 6 months of 2017.

“There is no legitimate medical use for kratom in the US,” the Drug Enforcement Administration (DEA) wrote in a report on its website. On August 16, 2016, the DEA announced its intent to classify kratom as a Schedule I controlled substance, noting that "kratom has been abused for its ability to produce opioidlike effects, and is often marketed as a legal alternative to controlled substances.”

Pharmacists should be aware of the substance so they can educate patients about the potential harms.​

Psychedelic medicine in the near future

Varanasi believes the importance of cannabis in pain management will only continue to grow. “Preliminary evidence demonstrates cannabis’ ability to provide significant pain relief as well as to help individuals taper off opioids particularly in the setting of addiction,” she said. “Though the research is inconclusive, patient anecdotes support the continued use of cannabis in pain management.”

In Oregon, the Oregon Psilocybin Program Initiative will appear on ballots in November 2020. “If passed, it would [be] the first state-sanctioned program for the administration of psilocybin services between a certified practitioner and a patient,” Varanasi said. “This would not only set the standard for other states but also support published studies reporting that a strong patient-practitioner relationship improves overall health outcomes.”

In the meantime, patients and practitioners alike will have wait to see how these and other psychedelics will alter integrative medicine and the world of health care.

*From the article here :
 
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Pinwheel flower

A Natural Treatment for Chronic Pain

Luxembourg Institute of Health & The Center for Drug Discovery at RTI International | 3 Jun 2021

Conolidine, a natural painkiller derived from the pinwheel flower and frequently used in Chinese medicine, interacts with a newly identified opioid receptor that regulates natural opioid peptides produced in the brain.

Building on their previous findings, scientists from the Immuno-Pharmacology and Interactomics group at the Department of Infection and Immunity of the Luxembourg Institute of Health (LIH), in collaboration with the Center for Drug Discovery at RTI International (RTI), a nonprofit research institute, have demonstrated that conolidine, a natural painkiller derived from the pinwheel flower and traditionally used in Chinese medicine, interacts with the newly identified opioid receptor ACKR3/CXCR7 that regulates opioid peptides naturally produced in the brain.

The researchers also developed a synthetic analogue of conolidine, RTI-5152-12, which displays an even greater activity on the receptor.

These findings, which were published on June 3rd in the prestigious international journal Signal Transduction and Targeted Therapy, further advance the understanding of pain regulation and open alternative therapeutic avenues for the treatment of chronic pain.

Opioid peptides are small proteins that mediate pain relief and emotions, including euphoria, anxiety, stress and depression, by interacting with four classical receptors (“molecular switches”) in the brain. Dr Andy Chevigné, Head of Immuno-Pharmacology and Interactomics, and his team had previously identified the chemokine receptor ACKR3 as a novel fifth atypical opioid receptor, with high affinity for various natural opioids.

ACKR3 functions as a ‘scavenger’ that ‘traps’ the secreted opioids and prevents them from binding to the classical receptors, thereby dampening their analgesic activity and acting as a regulator of the opioid system.

In the current study, the researchers identified ACKR3 as the most responsive target for conolidine, an alkaloid with analgesic properties, by screening over 240 receptors for their ability to be activated or inhibited by this molecule.

“We confirmed that conolidine binds to the newly identified opioid receptor ACKR3, while showing no affinity for the other four classical opioid receptors. By doing so, conolidine blocks ACKR3 and prevents it from trapping the naturally secreted opioids, which in turn increases their availability for interacting with classical receptors. We believe that this molecular mechanism is at the basis of the beneficial effects of this traditionally used medicine on pain relief,” said Dr Martyna Szpakowska, first author of the publication and scientist within the LIH Immuno-Pharmacology and Interactomics group.

In parallel to characterising the interaction between conolidine and ACKR3, the two teams went a step further. The scientists developed a modified variant of conolidine — which they called “RTI-5152-12” — which exclusively binds to ACKR3 with an even higher affinity.

Like LIH383, a patented compound previously developed by Dr. Andy Chevigné and his team, RTI-5152-12 is postulated to increase the levels of opioid peptides that bind to classical opioid receptors in the brain, resulting in heightened painkilling activity.

The LIH-RTI research teams established a collaboration agreement and filed a joint patent application in December 2020.

“The discovery of ACKR3 as a target of conolidine further emphasises the role of this newly discovered receptor in modulating the opioid system and, consequently, in regulating our perception of pain,” said Dr. Chevigné, corresponding author of the publication and leader of the LIH Immuno-Pharmacology and Interactomics group.

“Our findings could also mean that conolidine, and potentially also its synthetic analogues, could carry new hope for the treatment of chronic pain and depression, particularly given the fact that conolidine was reported to trigger fewer of the detrimental side-effects — namely addiction, tolerance and respiratory problems — associated with commonly used opioid drugs like morphine and fentanyl.”

“Our work could therefore set the basis for the development of a new class of drugs with alternative mechanism of action, thereby contributing to tackling the public health crisis linked to the increasing misuse of and addiction to opioid drugs,”
says Dr. Ojas Namjoshi, co-corresponding author of the publication and lead scientist on the study at RTI.

“Once again, we have built on the findings of our excellent fundamental research and translated them into applications with the potential of tangibly improving clinical outcomes for patients,” said Prof Markus Ollert, Director of the LIH Department of Infection and Immunity.

 
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Hemp oil for pain relief*

by Debra Rose Wilson, Ph.D. | MedicalNewsToday | 14 Feb 2019

Many people use hemp or CBD oil as a form of natural pain relief, especially if the pain is a result of inflammation.

Those who do not want to take over-the-counter or prescription pain medications may turn to a high-quality hemp oil for relief.

A 2018 review notes that CBD, one of the main compounds in full-spectrum hemp oil, and other cannabinoids show promise for the treatment of many types of pain.

There is very little risk of intoxication from hemp oil as all forms of hemp oil come from food-grain strains of hemp. The authors of a study in the journal Cannabis and Cannabinoid Research note that food-grain strains of hemp must contain less than 0.3 percent tetrahydrocannabinol (THC). THC is the compound that causes the so-called “high” of marijuana.

Hemp oil is not the same as cannabidiol (CBD) oil. The production of CBD oil uses the stalks, leaves, and flowers of the hemp plant, which contain a higher concentration of CBD, another potentially beneficial compound in the plant.

Hemp seed oil comes from the small seeds of the Cannabis sativa plant. The seeds do not contain the same levels of compounds as the plant itself, but they still have a rich profile of nutrients, fatty acids, and useful bioactive compounds.

Full-spectrum hemp oil that also contains plant matter may add other effective compounds, which may help with certain health issues, such as inflammation.

Takeaway and future research

The research on hemp oil is still relatively new, particularly in the United States and other places where restrictive laws have prevented researchers from fully exploring the potential of cannabis plants until recently.

As CBD comes into more common use in an increasing number of areas, research into the potential benefits of full-spectrum hemp oil may expand. As a result, scientists may find more evidence to support the potential benefits of the plant or even reveal new benefits. In any case, the future of research on hemp oil looks promising.

There is also still a small risk of THC getting into the system, even from hemp seeds, which normally contain no THC. The THC could be present as a result of contamination with other plant matter. The results of a 2017 study show that some commercial brands of food-grade hemp seeds can have a THC concentration that is as much as 1,250 percent higher than the legal limit.

It is essential to ensure that hemp seed oil comes from a reliable manufacturer. The seeds and oil should be free of plant matter that may add additional compounds, such as THC.

*From the article here :
 
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Pain and psychedelics – 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.

 
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Researchers report 20 micrograms of LSD delivers similar analgesic results
to opioids such as oxycodone and morphine in an acute pain test.

LSD microdosing trial for acute pain relief reports remarkable results*

by Rich Haridy | NEW ATLAS | 26 Aug 2020

An incredible, first-of-its-kind trial testing the pain-killing properties of LSD microdoses has delivered the compelling suggestion that tiny, non-psychedelic doses of this infamous drug could serve as an effective analgesic.

Back in the 1960s, during the original heyday of psychedelic science, one of the more fascinating research areas for LSD was its unexpected efficacy as an analgesic. Researcher Eric Kast was one of the pioneer investigators on the topic, publishing over a dozen key papers exploring the ways pain perception is influenced by LSD.

Kast’s work was primarily with active psychedelic doses of LSD, and he consistently found the drug produced effective, and protracted, analgesic effects. Unfortunately, Kast’s work with LSD ended, as most psychedelic research did, when access to the drug was restricted in the late 1960s.

Decades later, as the freeze on psychedelic research begins to thaw, the idea of LSD as a pain-reliever still sits on the fringes of psychedelic science. No modern clinical researcher has returned to Kast’s ideas, however, anecdotal cases have begun to emerge highlighting some people self-medicating with LSD microdoses to treat chronic pain.

This new study, led by researchers from Maastricht University with assistance from the Beckley Foundation, is the first clinical trial to revisit this topic in more than 50 years. Unlike Kast’s prior work, this new research focused on microdoses of LSD rather than larger, actively psychedelic doses.

“From a medical point of view, controlled research on the efficacy of LSD in pain management should focus on non-hallucinogenic, low doses of LSD, which are more manageable and thus preferable over treatment with high doses of LSD that produce full-blown psychedelic effects,” the researchers explain in their paper.

The double-blind, placebo-controlled trial recruited 24 healthy subjects, each of whom took part in four separate experimental sessions, separated by at least five days. Three different LSD microdoses were tested (five, 10, and 20 micrograms) alongside a placebo.

During each experimental session, the subjects completed a Cold Pressor Test (CBT) at two time points following dosing: 90 minutes after and five hours after. The test basically involves plunging one’s hand into a tank of water at 3 °C (37.4 °F). Pain tolerance is measured by combining the amount of time one can hold their hand in the cold water, with a series of subjective ratings regarding painfulness.

The researchers described the results of the study as “remarkable”, with the 20-µg-dose group revealing prolonged improvements to pain tolerance compared to both lower doses and placebo. The results were sustained across both time points suggesting the analgesic effect is just as prominent five hours later as it is within the first 90 minutes.

“The current data consistently indicated that LSD 20 µg significantly reduced pain perception as compared with placebo, whereas lower doses of LSD did not,” the researchers write. “LSD 20 µg significantly increased pain tolerance (i.e. immersion time) by about 20%, while decreasing the subjective levels of experienced painfulness and unpleasantness.”

So what exactly is going on here? Is LSD just distracting people from the acute pain, or is it actually inhibiting pain signaling through a more direct pharmacological mechanism?

Kast hypothesized 50 year ago these analgesic effects were the result of LSD reorienting attention away from pain sensations to a more encompassing psychedelic experience. While that hypothesis certainly is reasonable when high LSD doses are administered, it doesn’t really explain the results seen in this new microdose trial.

The researchers do note a small correlation between increasing levels of psychedelic disassociation and greater pain relief in their results, but the association was weak. They estimate it accounting for no more than six percent of the variance in analgesic results.

A variety of possible alternate hypotheses are presented in the new study, from pharmacologically influencing specific brain receptors known to mediate pain sensation, to triggering a condition called hypertension-associated hypoalgesia whereby blood pressure rises can lead to a diminished perception of pain.

“… an extended dose-finding study is needed to determine the dose at which analgesic effects of LSD are optimal, i.e. when efficacy is maximal and mental interference is minimal,” propose the researchers. “Such a study could potentially explore the trade-off between increments in treatment efficacy and psychedelic symptoms in a low to medium dose range (i.e. 20–50 µg LSD).”

Perhaps the most intriguing finding in the study is the observation that the analgesic effect seen in the 20-µg LSD group is comparable to what prior studies have seen with in the same cold water pain test for opioids such as oxycodone and morphine.

Needless to say, a great deal more research is needed before these results can be extrapolated into any real-world clinical treatment. Will these LSD microdose results translate into pain relief for chronic pain sufferers? Or is this kind of analgesic best for certain types of acute pain? What are the safety issues surrounding long-term use?
Does a tolerance eventually build to low-dose LSD?

At the very least these promising results suggest further clinical trials are necessary as modern researchers slowly catch up with where the science was half a century ago.

The new study was published in the Journal of Psychopharmacology.

*From the article here :
 
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I can live again!

by Tim Riley | LDN Science | 1 Mar 2017

Low Dose Naltrexone dramatically reduced my severe chronic back pain, making opiates obsolete.

Please tell us a little about your health condition.

In 1998 I had 2 back operations that failed and left me in a lot more pain than ever. We're talking constant pain. Every 3-6 months, I'd see yet another doctor and do another procedure (epidurals, burning of the nerves, steroid injections). They did over 30 procedures on my lower back, but nothing seemed to work. I was in an incredible amount of pain.

What was your pain like before LDN?

It was constant and crippling. I'd wake up in the morning and think, Where is my medication? I'd have to pop a pill and wait 20 minutes for it to take effect in order just to get up out of bed. I had to hang onto things, like the countertop, in order to walk. It took me an hour to get going in the morning. I'm only 63 now but I felt like a very old man.

How did your doctors treat your pain?

The doctors put me on high doses of long-acting morphine, and short-acting and extended-release oxycodone. At one point, I would take 60 mg of long-acting morphine in the morning, another 60 mg again at night, and every 4 hours during the day I would take an oxycodone. Here I was taking all those heavy duty drugs, and my body was depending on them. 3 to 4 four hours after taking oxycodone, the pain would flare up again and Id feel like I needed to take it again.

Why did you want to get off opiate-based medications?

I was on those medications for 12 years. I was able to get off of them, but then eventually had to go back on them for another 5 years. A couple times the pain got so bad, I took more than my usual amount. But if you run out of your medication early and you need more (because you cant do without it), you are looked at like a criminal. It was so depressing. If you do one thing wrong, doctors will throw you out of their practice. First they tell you that you need morphine, and then, a year later, they are locking doors behind you. They are treating you like a criminal, requiring urine tests, and scrutinizing your every move. At one point, I couldn't stand it any longer. I was going to commit suicide. I wanted off those other medications.

How did you come to take LDN?

About 16 months ago, after telling my doctor I wanted to get off all opiates, he told me to go to a detoxification center that deals specifically with people with chronic pain. By giving me various other medications for different periods of time, they were able to help me get off all the opiates. As part of their treatment, they gave me shots of Vivitrol, and I started to feel much better. After a year, though, insurance no longer covered those treatments. So, I needed to find something else. I had been reading about low dose naltrexone and decided to pursue it. I found a doctor willing to prescribe 50 mg naltrexone pills to me that I dissolved in water, and I dosed myself with 4.5 mg of LDN each morning. I've been on LDN for about 3 months. I haven't felt this kind of pain relief in over 20 years.

How successful has LDN been in reducing your pain?

I have 75-80% less pain than when I was taking opiates. LDN is affordable and has virtually no side effects. Even with all that, its infuriating that most doctors aren't interested in it. I asked my doctors about LDN every now and then over the years, and they dismissed it, saying that it didn't work. But it does. Yesterday I forgot to take my LDN, and I started to feel the pain return. I took it this morning, and now the pain is gone.

Has LDN affected you in any other way?

I also have COPD, which is a lung disorder. I usually have 2-3 bouts with it during the wintertime, but this winter (since Ive been on LDN) I haven't had any exacerbations. Also, my mood is better. When I was on all those opiates, although I never allowed myself to get really depressed, I had to really fight becoming depressed. Now, because I'm in so much less pain, I don't have to struggle to stay positive.

You mentioned that you take LDN in the morning. Why?

I tried taking it at night, but I couldn't sleep well. So, I started taking it in the morning instead, and it worked just as well without any side effects at all. I could probably try taking it at night again and see if my body has adjusted to it already.

What's been the biggest change for you since starting LDN?

I can walk freely. I just step out of the bed, and I'm walking right away. Like normal. It's incredible. I could walk right across the street. My spine is like a disaster area, so that's really saying something. I'm not 100% pain free, but I can do a lot more than before. LDN has been amazing for me. I am now doing better than I ever was when taking all those heavy duty opiates. There's a radio commercial that says, When you're living on pain meds, you're not really living. I can live again!

What would you like to tell people in the same position as you once were?

If you're in chronic pain and you want to get off opiates, but you're afraid to, I'd recommend finding a detox program that deals with chronic pain patients. After you get off the opiates, I recommend you try LDN. Hopefully you'll get better pain relief than you ever had before. It might set you free.

https://www.ldnscience.org/resources...onic-back-pain
 
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Ketamine more effective than opioids for acute pain*

by Brandon May | Clinical Pail Advisor | 18 Dec 2020

Ketamine may be a more effective treatment option than opioids for prehospital acute pain, according to findings from a systematic review study published in the BMJ Open. Ketamine likely decreased pain more than opioids, but had a notable higher risk for agitation.

The review included 8 studies comprising a pooled cohort of 2760 adult patients with prehospital acute pain who were treated with either ketamine, opioids, or nitrous oxide. Studies included in this review were 4 randomized controlled trials, 1 cluster randomized trial, 1 prospective cohort study, and 2 retrospective studies.

Across studies, comparisons were made between intravenous (IV) ketamine and IV opioids, IV ketamine with IV morphine vs IV morphine alone, continuous IV ketamine vs single-dose IV ketamine, intranasal ketamine with nitrous oxide vs nitrous oxide alone.

According to the investigators, there were 5 studies in the review that had high risks of bias. In a cluster randomized controlled trial of 308 patients and a retrospective cohort of 158 patients, treatment with ketamine was associated with probable lower pain scores compared with opioids (change in visual analogue scale, prior to hospitalization}.

The researchers also found that treatment with ketamine probably led to less nausea and vomiting compared with opioids, but greater agitation.

A limitation of the study, according to the researchers, was the potential lack of other studies that may have generated more relevant results, including studies not published in English. Also, none of the studies included in the review were powered to assess the safety of ketamine in this patient population.

Based on this review, the researchers concluded that treatment with IV ketamine in analgesic doses of 0.1 to 0.2mg/kg “appears to be at least as effective as opioids administered alone considering pain reduction.”

*From the article here:
 
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Medical cannabis for chronic pain sufferers with Fibromyalgia*

by dispensaries.com | 23 Sep 2021

When it comes to the health benefits of cannabis, better pain management always ranks high on the list. It’s the reason many people turned to medical cannabis in the first place (often as a replacement for opioids). But it’s of special importance to those with Fibromyalgia.

Chronic pain is one of the unfortunate characteristics of Fibromyalgia, a condition that also causes fatigue, memory problems, and difficulties sleeping. Patients suffer from the condition without any well-defined, underlying organic disease, and the exact cause of fibromyalgia remains unknown.

A new literature review of 22 scientific papers conducted by the California Institute of Behavioral Neurosciences and Psychology investigated the use of cannabis or synthetic cannabinoids with fibromyalgia patients. They report that the studies “suggest that medical cannabis is a safe and effective treatment for Fibromyalgia pain,” although there are some limitations.

Fibromyalgia impacts between 5 and 7 percent of the population.

Millions of people worldwide suffer from Fibromyalgia. In the United States and Europe, about 4 percent of the population has Fibromyalgia syndrome (FMS), according to the study. About twice as many women as men suffer from the syndrome. FMS can develop at any age, and often happens in connection with rheumatic diseases.

Because so many studies have found that cannabis provides effective treatment for pain - and promotes better sleep - it’s often mentioned as a possible medication for FMS patients. A handful of studies have looked at the issue through the years. They include:​
  • A 2008 study involving 40 fibromyalgia patients that found the synthetic cannabinoid nabilone had significant pain-relieving effects​
  • A 2011 study involving 28 patients who used cannabis for Fibromyalgia and found that 43 percent reported strong pain relief and 43 percent reported mild pain relief​
  • In that same 2011 study, 81 percent of participants reported that cannabis provided strong relief from Fibromyalgia-related sleep issues​
The recent review, however, took a comprehensive look at a wide range of studies over the years.

For FMS suffers, cannabis can provide relief with limited side effects.

Essentially, the researchers found that previous studies make a strong case for further research into the treatment of Fibromyalgia pain with weed. The aim of the study was to explore the potential for cannabis use, and the researchers concluded that potential is high.

They wrote, “Ultimately, we believe that the use of cannabis and cannabinoids for pain relief in Fibromyalgia has shown great potential and may be a source of hope for those suffering from chronic pain associated with this condition, and for the physicians treating them.”

However, they also wrote that the benefits must be weighed against any potential harmful effects, calling for more research conducted for longer periods to assess the long-term efficacy of cannabis for chronic pain.

Authors concluded "cannabis carries limited side effects, and can also improve some common and debilitating symptoms associated with FM, thus making them an adequate potential treatment option, when other treatment lines have been exhausted.”

Interest certainly remains high among those with Fibromyalgia. A survey in Canada found that 24 percent of Fibromyalgia patients reported a history of cannabis use. Of those, 61 percent classified themselves as current marijuana users and many reported substantial symptom relief.

*From the article here :
 
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Iboga saved me from chronic pain

Most people are not aware that Iboga is profoundly effective for treating severe pain caused by nerve damage. The majority of people I've talked to have only heard of it for treating addiction. The reason I am writing this is because I suffered from debilitating pain that made me feel like my life was over. I lost hope. Before my Iboga experience this summer, I had absolutely no idea it would do anything for my damaged nerve. Little did I know. For three whole months after taking a good dose of Iboga, the noribogaine was still flowing in my body, and I was able to do things that I had not been able to do in a long time.

I had got it into my head that my nerve was damaged, and there was nothing I could do. It is hard not to when everything you try doesn't help or only makes it worse. After 3 months, I began to notice my symptoms were coming back because the noribogaine metabolite was finally being flushed from my body. I made a conscious decision to break away from the beliefs I had about myself and my situation.

So for the past month or so I have been taking ~1g of potent Iboga bark per week. It allows me to function on a level I never thought possible. I feel more like myself now than ever before. I can live and be happy and not even think about my nerve. I am doing more than I ever could before with this disability, and I feel like it's exponential, the more I do, the more I can do. It's an exercise. A constant process.

Iboga allowed me to take a step back into my self unadulterated by the constructs of my mind and start working every day to be the better person that I have always wanted to be. It feels odd saying this, but I feel Iboga saved my life. My work with it keeps evolving, too.

I recently gave up an 11 year cannabis addiction, as well as coffee and nicotine overnight with 1g of potent bark, good food, lot of water, and meditation. I did this because I always told myself I never could, or I never wanted to. I just got fed up. I've been perfectly happy, and sober (except for Iboga effects, which are mild), for the first time in my life. I honestly never ever thought this was possible and I am loving it. I am sure I will use cannabis again, but it feels good to take a break and not be dependent.

So, in conclusion, if you are in a country where Iboga is legal, and you suffer from chronic pain that nothing else seems to help, you may want to consider this medicine.

https://www.dmt-nexus.me/forum/defau...=posts&t=27827
 
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This is why Botanical Farms CBD Gummies contains a unique “water soluble” system. The technology is shown to improve absorption in the cells by 450%, quickly boosting the body’s cannabinoid levels.

“The other problem is that most of these formulas only contain a single compound extract,” says Ms. Kim. “CBD’s cannabinoids are shown to work synergistically. In short, they work better together.”

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Cassandra Healy, a 52 year old grandmother was one of the first users of Botanical Farms CBD Gummies.

"I was plagued by the symptoms of Fibromyalgia and arthritis. I couldn't get out of bed. I was in pain constantly. And the 'Cures' were worse than the symptoms. They had me on harsh drugs. I was bed-ridden and severely depressed. My life was over."

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*From the advertisement here (as seen on CNN) :

 
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Self-Medication for Chronic Pain using Classic Psychedelics*

Julia Bornemann(1), James B. Close(1), Meg J. Spriggs(1), Robin Carhart-Harris(1,2), Leor Roseman(1)

1Centre for Psychedelic Research, Division of Brain Sciences, Imperial College London, London, United Kingdom
2Psychedelics Division, Neurology, Psychiatry and Behavioral Sciences Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, United States

Background: Chronic Pain is among the leading causes of disability worldwide with up to 60% of patients suffering from comorbid depression. Psychedelic-assisted therapy has recently been found effective in treating a host of mental health issues including depression and has historically been found to be useful in treating pain. Reports of self-medication for chronic pain using psychedelic drugs have been widely documented, with anecdotal evidence indicating widespread success in a range of pathologies.
Aims: In preparation for an upcoming trial, to better understand how those with lived experience of chronic pain self-medicate with psychedelic drugs, and to establish, in detail, their therapeutic protocols and practices for success.
Methods: As part of patient-involvement (PI) for an upcoming trial in this population, 11 individuals who reported self-medicating with psychedelic drugs took part in a 1-h semi-structured discussion, which was then transcribed and thematically analyzed.
Results: Across a range of psychedelic substances and doses, reported pain scores improved substantially during and after psychedelic experiences. Two processes, Positive Reframing and Somatic Presence, were reliably identified as playing a role in improvements in mental wellbeing, relationship with pain, and physical (dis)comfort. Inclusion of other strategies such as mindfulness, breathwork, and movement were also widely reported. Due to the data's subjective nature, this paper is vulnerable to bias and makes no claims on causality or generalisability. Together, these results have been used to inform study design for a forthcoming trial.
Conclusion: This pre-trial PI work gives us confidence to test psychedelic therapy for chronic pain in a forthcoming controlled trial. The results presented here will be instrumental in improving our ability to meet the needs of future study participants.​

Introduction

Public and Patient Involvement (PPI) aims to produce research “by” and “with,” rather than “to” or “for” people with lived experience (NIHR). PPI is effective across health research (1, 2), particularly in mental health research (3, 4), and is an emerging topic in the psychedelic field (5). By incorporating non-researcher, e.g., patient and public input into various parts of the research cycle, PPI produces relevant, transparent, and accountable research (6, 7). This PPI venture was undertaken to involve people with lived experience (“contributor”) in the design phase of a future trial investigating the effects of psilocybin in people with fibromyalgia. The fibromyalgia population was chosen for potential psychedelic application because of its relatively common occurrence, central nervous system involvement, and high rates of mental health co-morbidities.

Those living with chronic pain report feeling misunderstood and invalidated (8, 9). This highlights the need for intentional communication at early stages of research to ensure thoughtful design that prioritizes the specific needs of people with chronic pain. The accordingly selected methods of in-depth, open-ended discussions (10, 11) and the thematic analysis thereof (1, 1214) are widely used in PPI. Further, such conversations effectively facilitate early involvement at the design stage of research (10, 15). The product is a nuanced exploration of the chronic pain experience and warrants the following background to adequately contextualize.

Roughly 20% of the global population live with chronic pain (16), and it is considered one of the global leading causes of disability (17). Chronic pain is defined as pain lasting over three months and may remain even if the original injury has formally healed (18, 19). Common chronic pain conditions include Chronic Low Back Pain, Headache, and Chronic Widespread Pain e.g. Fibromyalgia Syndrome. Living with chronic pain significantly impacts a person's ability to work, resulting in high levels of lost productivity, reportedly costing the UK economy £10.7 billion annually (20). The social implications of chronic pain are also considerable; over half of pain patients report that their condition has prevented them from seeing family and friends and that their pain contributes to significant social anxiety (21). Such increases in social isolation, as well as the general stress from constant pain, directly impact patients' psychological wellbeing; it is estimated that 20% of people with chronic pain experience comorbid depression (22), with rates up to 60% in conditions such as Fibromyalgia Syndrome (23). This well observed bidirectional relationship links stress to an increased likelihood of developing chronic pain (24, 25).

Current guidelines recommend education, physical therapy and pharmacological interventions, such as non-steroidal anti-inflammatory drugs (NSAIDs), weak opioids, and antidepressants or anticonvulsants off-label (26, 27). Second line treatments graduate to invasive procedures such as neurosurgery, neuromodulation, nerve blocks and radiofrequency denervation (27, 28). However, several problems with the current strategies for treatment of chronic pain remain. Firstly, existing medications carry a number of unwanted side effects and can be habit forming, for example long-term opioid use is linked to dependence and has directly contributed to the ongoing international opioid crisis (29). Secondly, conventional interventions, both pharmacological and invasive, have high Number-Needed-to-Treat values and are only effective in up to 80%, leaving ~1 in 5 sufferers without pain relief (30). Finally, these treatments either neglect or fail to adequately address the psychological impact of chronic pain conditions, leading to growing numbers seeking alternative treatments and experiment with self-treatment (31, 32). In cases where pain persists, patients can be referred to multidisciplinary pain management programmes (PMPs), which aim to support individuals to effectively manage and live with their pain through education, physical therapy and psychological therapies such as Cognitive Behavioral Therapy (CBT) (33) or Acceptance and Commitment Therapy (ACT) (34). CBT and ACT are well-established trans-diagnostic behavior-based psychological therapies which aim to improve awareness and reduce harm caused by negative thought patterns. Their shared foundation focuses upon Cognitive Reframing/Restructuring, a process in which thoughts and beliefs are identified, examined, their relative importance is reviewed, and maladaptive beliefs are updated with therapeutically useful, often positive, ones (35). Evidence suggests such cognitive reframing is transdiagnostically useful, resulting in improved outcomes in healthy populations (36), depression (37), Post-Traumatic Stress Disorder (PTSD) (35), and chronic pain (38). While PMPs are the sole treatment option to directly address the prevalent mental health comorbidities associated with chronic pain, their efficacy is largely limited to the short term (3942) and attrition/relapse rates remain high (43, 44).

Used in combination with psychological support, psychedelic drugs [e.g., Lysergic Acid Diethylamide (LSD), Psilocybin (the psychoactive component of magic mushrooms), and dimethyltryptamine (DMT)] appear to exhibit promising therapeutic effects in conditions such as depression (4547), addiction (48, 49), and end-of-life anxiety (5053). The safety profile of psychedelics is well-established as largely physiologically benign (54), though psychologically challenging periods are common during acute experiences (55). Case reports of persisting perceptual changes exist, though these are rare (54, 55). Historically, there has been interest in using psychedelics to treat chronic pain; preliminary studies from the 1960s and 70s suggest that psychedelic drugs may be therapeutically useful, specifically for cancer pain and phantom limb pain (5661). Although the results of these historical trials all show promising results, they lacked the methodological rigor of modern trials making it difficult to draw strong inferences on their findings. Contemporary studies suggest that psychedelics may be therapeutically useful in treating intractable headaches such as migraine and cluster headaches (6264), and two recent reviews hypothesize potential mechanisms and applications for psychedelics in chronic pain (65, 66). Pharmacologically, this concept is plausible. The primary mechanism of action of classic psychedelics is via the 5-HT2A serotonin receptor, which is integral to inflammatory pain (67, 68). Data suggests that psychedelics reduce inflammation (6971) via the downstream effects of 5-HT2A agonism such as TNF regulation (72), and may result in desensitized central pain responses (66). The acute effects of psychedelics may also contribute toward an analgesic response by reorienting attention away from unpleasant sensations toward altered perceptions, e.g., visual hallucinations (73).

While research has stalled for decades due to the legal status of psychedelic drugs, public interest has not. Psychedelic self-medication has grown in popularity in recent years, reportedly making up 14.8% of self-reported psychedelic substance use (74) and first time LSD-use having increased ten-fold in 10 years in adults over 26 (75). Methods of use range from the semi-regular taking of sub-perceptible doses (known as “microdosing”) to isolated high dose sessions emulating clinical contexts to address mental health concerns (76). Notably, anecdotal reports of effective management of chronic pain have been prevalent; online forums such as Erowid and Reddit contain hundreds of reports of effective treatment for chronic pain conditions such as Fibromyalgia (ErowidFMS) (77, 78), Chronic Back Pain (ErowidCBP), and Rheumatoid pain (RedditEDS) (79). The largest group of reports concern chronic cluster headaches and migraines (80), with over 10,000 people participating in the organization “Clusterbusters,” dedicated to the treatment of headaches with psychedelics (81). This has given rise to a cache of largely untapped knowledge held by psychedelic users who, through self-experimentation and extensive online publishing of “trip reports,” have independently attempted to develop a public library detailing the effects of different substances. This PPI initiative takes advantage of existing public interest and knowledge with the objective of infusing context and input from people with lived experience into various aspects of trial development, and directly influence study design, therapeutic protocols, and outcome measures.
For this PPI investigation, 11 public contributors were invited for 1-to-1 open ended discussions with one of the researchers developing the upcoming trial. The aim of these discussions was to explore (i) how people with chronic pain self-medicate with psychedelic drugs, (ii) whether people have found psychedelics to be effective, and (iii) to gain some insight on specific practices that contributors feel are important for treatment success. While safeguards against bias were employed (see section Materials and Methods), we do not claim that the following work is free of bias or generalisable to the larger population.​

Materials and Methods

Public Contributors

Contributors with lived experience of chronic pain and alleged personal use of psychedelics as a self-medication attempt were recruited through online pain forums, e.g., Reddit, psychedelic retreats, and word-of-mouth. Online posts asked about experiences with psychedelic self-medication for chronic pain and whether people would be open to a discussion about this topic. In total, 44 people responded, and 11 agreed to a 1-h video conversation. The remaining 33 respondents did not contribute to this project because they either failed to reply to messages requesting a conversation, or did not appear at the agreed-upon meetings (3). Eight contributors were recruited from online forums, one was recruited through word-of-mouth, and two were recruited from psychedelic retreats via advertisements sent to retreat alumni email lists.​

Discussions

Discussions took place between April and June of 2020 and lasted between 55 and 90 min. Consent was given to record, analyse, and use data obtained from discussions in analysis. Discussions were semi-structured and spanned three major topics: a background of their pain, their psychedelic use, and whether and how psychedelic use may have been effective for their chronic pain. This open-ended approach was chosen to capture a range of responses and reduce interviewer bias. All contributors were asked to rate their pain at various timepoints according to a Numerical Pain Rating Scale (NPRS) from 0 (No Pain) to 10 (Worst Imaginable Pain) (82). The common interpretation of this rating scale is that pain scores of 1–3 are considered to be mild, 4–6 moderate, and 7–10 severe. If contributors reported multiple experiences, their most impactful experience was selected. Contributors were asked to rate the pain that they experience (1) on an everyday basis, before they began self-medicating with psychedelics, (2) their pain during the acute experience, and (3) after they self-medicated with psychedelics (see Figure 2). Discussions were recorded and transcribed.​

Ethical Approval

The Imperial Research Governance and Integrity Team (RGIT) was informed of all planned activities of the following project involving human PPI contributors. This project was undertaken as PPI and RGIT confirmed that ethical approval was not required. During conversations, PPI contributors provided verbal informed consent to participate in this study.​

Data Analysis

We used qualitative methods to derive major trends across contributors. To obtain an unbiased view of the data, thematic analysis followed an inductive coding approach (83), allowing themes to arise from the transcriptions themselves, and minimizing confirmation bias. Analysis was undertaken on each data set and created initial codes. Once a first set of codes was established, the sample set was re-analyzed, updated codes were produced, and themes were determined. Subjectivity was addressed by cross-referencing for inter-coder reliability and the final set of themes was confirmed. From this, the themes were categorized into Pain Disability/Debilitation, Acute, and Enduring Change categories and configured into a hierarchical coding frame to establish the relative importance of each theme. This produced major and minor themes. Themes were considered major if they appeared in at least four discussions. There were several major themes which contained several sub-themes.

To establish the relationships between themes, one matrix was created for all contributors and themes, and the presence of each theme was detailed. The relative strength of connection between themes was established through the co-occurrence of themes, which were coded by frequency. These connections were noted and mapped onto a network graph using open access software (Figure 1) (84). No quantitative, statistical analyses were undertaken as the values reported were retrospective, and the main aim was to explore relationships between themes. Therefore, the following serves as a commentary on how themes were interrelated and makes no inferences about causation.

FIGURE 1
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Figure 1. An example of how relative connection strengths were mapped on a network graph, in this case regarding pain reduction. The full, interactive graph is available here: https://public.flourish.studio/visualization/6283835/.


FIGURE 2
fpsyt-12-735427-g002.jpg

Figure 2. Retrospective Numerical Pain Rating Scores from each contributor before, during, and after the psychedelic experience. The perceived intensity of pain was considerably lowered during the acute psychedelic state and slowly increased to the normal level over a period of hours to days. We make no inferences on causality from these retrospective subjective data.​

Reporting​

This investigation followed GRIPP2 guidelines for reporting PPI (85). PPI was undertaken at the planning stage to influence the design of our study. Contributors were not paid for their involvement.​

Results

Demographics of the six women and five men (range = 21 and 52, mean = 34, SD = 9.7) years of age) who took part in these conversations can be found in Table 1. Ethnicities were slightly over-represented when compared to the UK national population. Contributors had mixed chronic pain, six of which reported more than one contributing condition. Contributors had been living with their pain for between two and 25 years (mean = 10.7, SD = 9) and tried between two and 14 pain treatments (mean = 6.6, SD = 4.4) with largely unsatisfactory rates of success. All contributors had previously received pharmacological treatment, and three pursued more invasive treatment such as radiofrequency ablation and surgery. All contributors reported co-morbid depression that was perceived to be closely linked to the intensity of their pain. Histories of psychological treatments were not provided.

TABLE 1
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Table 1. Summary of contributor demographics.

Substances, Doses, and Frequency-of-Use​

There was considerable variation in substances, doses, frequency-of-use, and the longevity of effects reported (see Table 2). This is likely due to the lack of research on the subject, as well as the absence of any guidelines due to legal status, leading contributors to experiment and create unique “treatment plans.” These plans were largely the product of trial-and-error, especially in regard to substance and dose.
TABLE 2
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Table 2. Summary of substances, dose, supplementary treatments, and pain responses.

As shown in Table 2, the substances used ranged, the most reported being psilocybin-containing mushrooms. Although not a serotonergic psychedelic and therefore not included in the analysis of this project, three people also reported using ketamine. There was also a wide range in precision, dose, frequency, and lifetime use; all reported taking at least one “high” dose of psilocybin, the estimated mean of which was 2.6g (SD = 0.5). High doses were largely taken on an as-needed basis, typically separating doses by several months. Some (5) also reported microdosing, on average twice weekly, with psilocybin (n = 3; mean dose = 225 mg; SD = 127.5) and LSD (n = 2; mean dose = 10 μg; SD = 5). Lifetime use ranged from 1 to >50 experiences.​

Pain and Effect of Self-Medication on Pain

Retrospective baseline pain severity (NPRS) scores ranged from 4.5 to 10/10 with a mean score of 7.25/10, implying severe chronic pain. All contributors reported a change in pain scores during the acute experience; nine reported pronounced reductions while two reported a short-term amplification of pain. Of those who reported a reduction in pain, the mean was 0.33/10. Finally, contributors were asked to rate their everyday pain after starting to self-medicate with psychedelics, focusing on the immediate period after the acute psychedelic effects had subsided, i.e., the following 48 h. Scores ranged from 0 to 8, with a mean of 2.73/10, implying mild pain. For most (7), this was followed by a gradual return toward baseline pain scores over a 2–5 days. The two who reported an increase during the acute experience reported a return to baseline pain scores following the experience. Given the exploratory nature of these data, it is not possible to determine the impact of different substances or dosing regimens to the changes in pain score.

The period of direct pain relief ranged from none (2) to 6+ months (2) (mean = 36, median = 7 days, SD = 67.9). Following thematic analysis, effects were split into somatic, i.e., analgesic, and psychological relief. In most cases, perceived longevity of “analgesia-like” pain relief was much more homogenous and ranged from 3 to 7 (mean = 5.4, median = 7, and SD = 2.9) days. Psychological effects were longer lasting, with four contributors reporting changes lasting for several months. One contributor was “not certain” of longevity, and six contributors reported that psychological changes had endured indefinitely after beginning their self-medication. Most contributors spontaneously reported that they hoped that psychedelic-assisted therapy be included in the future canon of pain treatments.​

Thematic Analysis

Thematic Analysis revealed three major categories of themes relating to Pain Disability/Debilitation, Acute experience, and Enduring changes. Each category contained major and minor themes. Larger major themes were split into several sub-themes. Themes are reported by major category of change, either “Positive Reframing,” or “Somatic Presence.” The final categories and contained themes and sub-themes are outlined below (Table 3). Interactive network graphs detail the relationships between all major themes are available here: https://public.flourish.studio/visualization/6283835/ (see Figure 1). Themes are described below with quotes from discussions:

1. Positive Reframing: This category describes contributors' psychological journey from depression, hopelessness, and pain catastrophising toward subjective experiences of acceptance and empowerment. Shifts toward perceived optimism and mental wellbeing were reported after psychedelic use and contributors described viewing often-unchanged situations, e.g., their life and pain, from hopeful and compassionate perspectives.

1.1 Pre-dose Impact of Pain: This category encompasses themes that contributed toward the burden caused by pain before psychedelic self-medication and provides context for the changes observed afterwards. While the physical and mental aspects of this category are invariably intertwined, this section will focus on the latter only. The quality of life of contributors was severely compromised by pain-related pessimism which affected their motivation and perceived ability to regain health. The following quotes suggest that the psychological strain of chronic pain was at least as impactful as the pain itself.

1.1.1 Depression: All contributors reported feelings of depression as part of their everyday life. While some contributors reported feelings of depression preceding their pain (5), all reported that their mental wellbeing and subsequent depression were impacted by the chronification of their pain. Several contributors (3) reported feeling suicidal due to their pain. Contributors reported feelings of hopelessness (7), frustration (7), distress (4), anxiety (9), defeat (4), anger (7), pain feeling all-encompassing (6), and lack of control (9).

It's easy to feel super defeated when you can't do anything… It feels like my life is a candle and I'm just watching the best part of my life burn away in front of my face and I can't really do anything about it”—C7.

[After diagnosis, I thought] I'm going to die a painful death and my life is going to suck. Woe is me, I'm not going to make it to 60… I was overloaded with sadness”—C3.

I just remember feeling really frustrated that I was in this situation. ‘When will it end, when will I feel normal again?'… I felt like I was my pain was controlling my life. There's some hopelessness in that… (I) legitimately thought I was probably never going to get better, or that I would never feel true happiness again, or comfort, or any of those things”—C11.

1.1.2 Interference with Lives: Pain interfered with the progression of the lives of all contributors, in the realms of career (7), relationships (3), and mood (10). This contributed to perceptions of hopelessness and a lack of control described above.

1.1.2.1 Psychological Disposition. Ten contributors reported a link between their pain intensity and their psychological disposition and mood. Of these, seven reported that specifically stress, both chronic and acute, contributed to pain severity. Acute stress worsened pain for six contributors and contributed to feelings of overwhelm. Five contributors reported that they felt chronic stress contributed to the development of their pain.

When I've had breakthroughs in my therapy, the pain has gone down. That's probably the biggest correlation between my trauma and my pain”—C1.

There was, and still is, a very clear correlation between my stress and emotional state and my level of pain”—C11.

I notice (the pain) more in the times when I'm really stressed out”—C4.

1.1.3 Loss of Identity: Seven contributors reported, to varying extents, feeling as though they lost part of their identity due to their pain. Contributors reported a change in personality due to medication (2), feelings of dissociation (4), and inability to perform activities, e.g., sports that were previously integral to their life and identity (3).

(Diagnosis) was really challenging. I worked closely with my therapist, and it was like navigating the different stages of grief… When I was diagnosed, to me it felt initially like my whole life was over. I didn't know what my identity was anymore…I wasn't sure if I was going to be wheelchair bound, if I was going to lose the use of my legs, what my life was going to look like”—C3.

1.1.4 Desire for Escape: Three contributors reported feeling a desire to escape from their pain and their body, ranging from desperation for relief to dissociation.
I just want a break; I just want to be happy. I'm so depressed. I don't want to be like this. How do I get out of this?”—C3.

1.1.5 Self-Punishing: One contributor used pain as a form of self-punishing by intentionally exposing themselves to known triggers.

If I feel like I haven't been my best self, if I feel like I'm not following my truth on some level. I think it can flare up in that context as a reminder, as a punisher in a way”—C5.

1.2 Post-dose Enduring Change: All contributors reported enduring changes in perspective, specifically positively reframing their relationship to themselves and their pain. Agency, acceptance, hope, and confidence were recurring factors in improved pain management and general wellbeing.

1.2.1 Mental Wellbeing: All contributors reported an increase in mental wellbeing. Consistent with literature (47), they particularly reported antidepressant and anxiolytic effects.

I legitimately considered killing myself a few weeks ago. I feel like my life has been saved… I have more of a will to exist now”—C7.

Every time I've done (mushrooms), it's always reminded me that there's a light at the end of the tunnel, that (the pain) might suck, but it's not that bad. It's totally manageable, I can be happy while all of this is going on”—C3.

Trying to focus on the positive and being grateful and being aware of all the wonderful things that are going on in their life. That really does make a huge difference for me”—C2.

1.2.2 Acceptance of Pain: Seven contributors reported increased acceptance of their situation and found this to be helpful in their general experience of pain.

I do feel differently about it. I also think differently about it… I'm able to say, yes, (pain) is something that I deal with. And yes, it sucks. And yes, I don't have the resource to do anything about it right now, but I'm doing what I can, and I'm still here, and I'm still alive. And it's not really that bad. I'm able to look at it differently, and that has a big effect”—C4.

1.2.3 Increased Agency: Seven contributors reported feeling more in control over their pain and life.

I still experience pain, but I experience it differently… Since I started microdosing mushrooms, I feel like it almost slows me down. I still have the same life stimuli coming at me, that hasn't changed, but it's allowed me to slow down and analyse the stimuli and then really think about how I want to react to it. That's the same with my pain. When I have a flare up of my pain, I really do feel like it's allowed me to have a little more time, or maybe thought space to process. I think, “Okay, you're hurting. What are the reasons? Is it because you did too much exercise or you sat down too long or is it emotional or stress based? How are we going to deal with this?”—C11.

1.2.4 Committed Action: Four contributors reported feeling increased motivation and dedication to take care of themselves and their health.

That experience inspired me to do things that would make me feel better and in turn feel less pain”—C6.

There are things in life that are also contributing to your experience of life. If you are dealing with issues that add to your emotional pain, those things don't lead you to go to the right state of mind… I use the psychedelic experience to cultivate more of the thoughts and feelings that I want in my life… If you are in the right state of mind, you do the things that help with your pain, like eating well, like practicing yoga every day. It impacts a lot of things in your life that will help in the long run with your battle with pain”—C8.

1.2.5 Increased Compassion: Eight contributors felt more compassion toward themselves (6) and others (5).

I think the biggest take-away for me was the knowing that I am good… I think that insight turned into compassion for myself ”—C9.

Now we've had this huge stress with COVID, I think I've been able to cope a great deal better. Having started the year with the psychedelic experience makes you incredibly more compassionate and connected to others, which is a huge resource in a time like this to tap into”—C5.

1.2.6 Increased Hope: Four contributors reported feeling more hopeful.

For me, it was really about hope. Trying to trust that what my brain was telling me wasn't permanent—the depressive thoughts, the awful feelings, how uncomfortable I am. There are ways for my brain to decipher that in a different way. The psychedelics are the hope of that things might be different, they might be better, and my brain might not interpret such awful discomfort. It's that moment of hope, of thinking I might be able to get my abilities back”—C3.

1.2.7 Connection: Psychedelically induced connectedness has been described extensively in existing literature as an essential mediator of wellbeing (86, 87). All contributors claimed feeling more connected, particularly to themselves. Many also felt connected to others (8), nature (4), and spirituality (4). All feelings of connections began in the acute experience and endured beyond.

1.2.7.1 Self: All contributors claimed feeling more connected to their sense of self. This included connection to emotions (4), intuition (3), inner child (1), a sense of identity (5). This self-connectedness contributed toward overall reframing by nurturing perceived self-belief and empowerment (see above), which improved their ability to manage their pain.

The experience allowed me to sure up a little bit my own personal view of myself... The truth rained down that I'm a good person. I just wasn't convinced of that before… I was able to undo that sense of being a curse”—C5.

(Psychedelics) always change my perception of myself. And my self-esteem. Always. I don't think it's inflated, but it goes to normal”—C9.

2 Somatic Presence: This category explores contributors' physical experiences, and mindfulness thereof. There emerged a repeated narrative from disability toward reduced pain and increased function. The process remains unclear but acute reports of perceptions of both embodiment and physical catharsis are repeatedly implied as possible contributors to change.

2.1 Pain Disability: This category describes the severity of day-to-day impairment contributors experienced due to their pain and serves as a counterpart to the previously described psychological measures. Again, this section provides a useful background for the striking outcomes reported.

2.1.1 Severe Pain: All contributors experienced severe day-to-day pain which felt “overwhelming” and generally remained “no matter what” contributors did.

It feels like someone is holding (a branding iron) on my body for the duration of my life”—C7.

It's the kind of pain where you're rocking back and forth, unable to handle it… (It) feels like my body is on fire...It feels like every cell is burning, but at the same time is dehydrated and going through radiation. It kind of feels like a sunburn, but not just on the skin level”—C10.

2.1.2 Physical Impairment: All contributors claimed physical impairment in the form of general functioning (11), sleep (7), or through the failure of previous treatments (7). Contributors claimed feeling disembodied and exhausted by their pain, both physically and emotionally, and felt “desperate” for relief.

2.1.2.1 Sleep: Seven contributors reported their pain affecting their sleep with severity ranging from difficulty sleeping (5) to not sleeping for several days (2). Beyond sleep, most contributors (10) reported feeling fatigued from the pain.

I was going for days without really sleeping and trying to find a comfortable way to sleep”—C11.

I couldn't even sleep, I literally could not sleep…I could handle the pain for the most part. It's just pain. But when I can't sleep at all, that's just something else entirely”—C7.

The fatigue was to a point where I needed help getting out of bed”—C10.

2.1.2.2 Function: General functioning was impaired for all contributors. This encompassed several realms, including eating (2), ability to do household work (3), moving around (7), getting easily triggered from the environment (1), memory loss (3), developing tics as coping mechanisms (2), and loss of independence (2).

I didn't cook dinner for my children for over a year. I couldn't run errands or drive. The pain is debilitating”—C11.
I can't walk and can't move... It gets to the point where I can't move an inch… it just feels like I'm on fire. It just won't stop no matter what I do. Recently, even just laying there hurts, everything hurts: walking, going to the bathroom… I can't even go to the grocery store”—C7.

2.1.2.3 Failure of Previous Treatments: For many contributors (7), treatment added considerable strain to their lives. Out of six contributors who had previously been prescribed opioid medication, two reported fear of treatment due to addiction potential and therefore abstained, and two reported developing an opioid dependency which had serious negative impact on their life. For other medications, contributors reported medication impacting cognition (1), worsening symptoms (4), and ability to stay awake (1). Five contributors reported medication either never working (3), or reducing in efficacy over time (2), effectively leaving them without options. Five contributors either underwent (2), or were expecting (3) surgery, with one contributor reporting considerable side effects thereafter.

I think over time my pain increased with the more opioids I took… I had no idea that I had become dependent... After taking myself off opioids and making it through the withdrawal symptoms... I was suffering from acute depression and anxiety in addition to my pain condition It spiraled me into a depressive state…I feel like (opioids) fucked with my head, made me a different person”—C11.

(On Prednisone) I was literally screaming myself into headaches and grinding my teeth smooth all night for weeks trying to sleep and (it) did not help (the pain) at all. Life was getting worse every day”—C7.

(Gabapentin and Lyrica) make me flighty, and I forget things—that's not my personality at all… (They) made my mind go. It was like I was a dementia patient”—C3.

2.2 Acute: During the psychedelic experience itself, contributors reported changed perceptions of pain mostly through analgesia (9), though two contributors reported subjective pain amplification. The process by which this occurred is not clear, though both active and passive processes were implicated in outcome. Varying degrees of physical catharsis (11) were observed, which were often induced or enhanced through intentional focus on the body and breath.

2.2.1 Acutely Forgetting Pain: Most contributors (9) reported reduced pain during the psychedelic experience that took form as complete (9) or partial (5) analgesia.
(Acutely,) I don't think of my pain any longer...I don't focus into pain because it's not there”—C8.

I felt zero discomfort in my body. I really didn't even think about my pain throughout my experience, which was really remarkable”—C11.

I remember getting up… and just being absolutely painless… I was standing up, perfectly upright, straight. Normally I can't put any pressure whatsoever on the right side of my body… I use crutches and canes most of the time, but I haven't for a few days”—C7.

2.2.2 Feeling of Health: Nine contributors reported a restored perception of health in their body. While descriptions largely related to the body, 10 contributors also claimed to feel mentally healthy. As with previous themes, the distinction is not clear as many contributors viewed health as including both body and mind (a continuous theme—see “Embodiment”).

My body felt amazing. It felt normal, it felt healthy… Like taking a deep breath and just letting it out and this full body feeling of euphoria”—C3.

My back was starting to feel like my other muscles, which is a huge difference for me…That's like when I'm on DMT—it feels normal, which is such a foreign word to my mouth to just feel normal”—C4.

2.2.3 Pain Amplification: Pain was amplified acutely for three contributors who all found the experience to be distressing. Contributors reported increases in pain and sensitivity at moderate and high doses (2), benefitting in spite of the pain (2), and that this amplification was only experienced at an extremely high dose and was contrary to previous experiences (1).

I was focused on my pain and I realized that there's nothing I can do. I was going in there deeper and deeper, and I was just feeling it more and more and it was really painful but I couldn't actually get to the source of it for some reason. So that's when I realized thatokay, this is serious, I have to seek help.' That was my actual reason for seeking help”—C1.

2.2.4 Physical Release: All contributors reported some form of perceived physical release through crying (3), tingling (5), vocalization (2), change in temperature (1), and release of muscular tension (5).

I noticed that while on mushrooms, I could actively feel where there's tension in the body. In yoga, or any practice for healing, they talk about breathing into that space, relaxing that space. I felt I was actually able to do that on the mushrooms”—C9.

2.2.4.1 Somatic Discharge: More violent expressions of physical release were considered as somatic discharge (2), defined as the process by which trapped emotions are discharged from the body in a cathartic expulsion (88).

I felt this intense welling of energy starting from the core of my body and it started to overtake me… (I) started crying, breaking down, just letting it all go, howling in agony and all this suffering I was just letting it out… I allowed it to take over, my body was moving, writhing and squirming… My entire body was tingling and felt really light and I felt so relaxed and completely pain free… It was the biggest release of my life… I got to let go of so much grief, fear, and even some anger. It's like every single cell in my body is just experiencing bliss, all at once. I really felt healed”—C6.

2.2.5 Working with the body: Eight contributors reported actively working with their body through focused attention (4), breathing (4), visualization (5), and movement (4).

I was laying on the floor and just breathing in different spots and feeling the energy in my body. I had more access to breath and (was) able to breathe into the spot and to actively feel the muscle, almost visualizing the muscle, and watching it release”—C9.

2.2.6 Breathwork: Four contributors reported using a form of breathwork alongside their psychedelic use.

When I'm breathing, I can feel my whole body is vibrating everywhere except for that one spot… when it lets go, it releases any kind of pain that I have”—C2.

2.3 Enduring Change: All contributors perceived lasting improvements in their overall quality of life. Most contributors also felt reduced pain (9) beyond the acute psychedelic experience, and persistent increases in embodiment (9), both contributing toward effective pain management and overall comfort.

2.3.1 Pain reduction: The majority of contributors (9) experienced a lasting pain reduction, though the length of this varied considerably.

Every time that I have taken LSD, I have experienced relief the next day. Every single time… it helps with my state of mind the following days, but the pain specifically, I feel it always. I always get some relief. Always”—C8.

I was waiting for (the neuralgia) to show up and it didn't. A month later, I literally fell flat on my face and had a concussion, but I did not have the neuralgia… Any kind of small accident that could affect this sphere would usually trigger the [chronic] pain and here I had a major accident and no [chronic] pain… Having a concussion and not having 3 months of neuralgia afterwards was unthinkable”—C5.

I think the (hydromorphone) was the most effective painkiller, but even when I took that, I remember it hurting a lot the next day, and needing another one just to get out of bed. It was a sacrifice. I equate (hydromorphone) to putting your phone on vibrate—it's still ringing, it doesn't mean it's off. But the mushrooms turned the phone off. It's not masking my pain in any way. It took (the pain) out back and shot it, and I'm good now”—C7.

2.3.2 Quality of Life: All contributors claimed improvements in their quality of life. This presented itself through increased function (5), independence (1), energy (5), and ability to move (4). Two contributors also reported perceived enhancements in cognitive performance (2). This contrasted with the extent of disability initially claimed and affected contributors' overall perceived wellbeing.

I am able to sleep, move, cook, use the bathroom, etc. I have regained mobility I have not had for years and am still in complete disbelief… I've had full mobility… I felt unusually fine ever since… It feels like my body time-machine-reverted all the way back to (when I was healthy) … I thought, maybe I can have a life again, and I laid there for maybe an hour just thinking about all the stuff I could potentially be able to do again”—C7.
It's made me more creative and able to respond and get out of my comfort zone… I've been able to read two books a week, so I definitely feel like it's boosted my brain”—C5.

2.3.3 Embodiment: The psychological construct of embodiment highlights mind-body connection and suggests subjective phenomena including feelings and behaviors are foundationally somatically informed (89). Here, the term specifically refers to this perceived connection. Both acute and enduring increases in embodiment were felt by nine contributors, departing from the dissociation and avoidance previously claimed (3). Acutely, contributors noticed this through intentional focus (4), newfound ability to move (5), and internal awareness (3). Enduring changes manifested as feelings of physical presence (7) and internal awareness (3). One person reported somatic discharge during the process of integration.

(I am) becoming present to my body, becoming present to the moment… becoming more aware of the relationship between how I feel and the pain that I feel”—C6.

I'd say that the way I could feel my body was heightened. It was the presence in my body. I feel like these drugs put me in my body. I think the only way you can feel your body is when you're in it. Then you actually can feel your pain and then release it, rather than being out of the body. I think they've made me more present and in being present I was able to pinpoint exactly where the pain is”—C9.

(I felt) the tissue memory percolating out. It really allowed this mobilization of trapped memories, the tissue memory of these trapped experiences to come out, but it did not come out during the trip, it came out as part of the processing and integration afterwards”—C5.

TABLE 3
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Table 3. Summary of categories, themes, sub-themes, and frequencies.


Discussion

This project was undertaken as a PPI venture for an upcoming trial, aimed at learning from the lived experiences of people with chronic pain and leveraging these data toward the development of trial design and procedures. To our knowledge, this is the first work detailing PPI for chronic pain in the context of psychedelics. Using thematic analysis, we highlight some common factors that contributors referred to as being linked to perceived successful outcomes from their self-medication. These were: positively reframed perspectives and strengthened sense of embodiment, as well as incorporating adjunct approaches. In interpreting these results however, we recognize that this work is subjective in two respects: (i) qualitative analysis is inherently subjective (90) which (ii) rests upon the subjective reports of, in this case, highly motivated contributors.

Broadly, the following are recommendations that can be taken forward from these reports into the development of the upcoming trial. Adequate preparation was highlighted as essential and included understanding the potential intensity of the experience, both physically and emotionally. All contributors in some way underscored the importance of trust, surrender, or openness for a beneficial outcome [see (91, 92)]. This included openness to the experience itself and contributors especially emphasized developing rapport and trust with their “guides” if used clinically (9397). Using additional modalities (see below) was also viewed as a key component of the experience. Although the specific choice(s) varied between each contributor, intentionally engaging with the body through movement and/or breath was frequently highlighted. Physical catharsis, whether through physical movement, somatic discharge (see below), or even through art was also valued. This will be incorporated into the trial (details below). Finally, integration and aftercare, while not reported by everyone, were viewed as essential to the perceived longevity of therapeutic benefit.

A common psychological component seen in those with chronic pain is pain catastrophising (98). Core aspects of this phenomenon were widely expressed by contributors and include a tendency toward pessimism, helplessness, and fear (99), the result being exaggerated experience of overall discomfort. Individuals with chronic pain judge the potential threat of pain through magnification and rumination, eventually compromising their perceived agency over their situation (100). Evidence supports a causal relationship between catastrophising and pain, to varying degrees (101105). There is also a known relationship between catastrophising and depression (104, 106) and tolerance of uncertainty (107, 108), and negative mental affect has widely been linked to worsened pain outcomes (25, 106). There can develop a self-potentiating or self-fulfilling cycle, in which the continuing experience of pain seemingly verifies the negative expectations that contribute to its maintenance. This is diametrically opposed to the tenets of optimism (109), hope (110), and openness (111) that characterize mental wellbeing, as well as improved core pain outcomes (112114). This trend, as well as the above recommendations concerning rapport, informed our preparation process which will now include added time and additional resources.

In addition, many contributors suggested some degree of cognitive reframing, with perceived psychological states shifting from overwhelming depression, disempowerment, anxiety, and hopelessness, toward connection, acceptance, agency, and hope. This transition from catastrophising toward clarity, and in most cases, perceived optimism, reportedly ameliorated contributors' perceived ability to effectively manage their pain; they described feeling more “prepared” and no longer overwhelmed. These results speak toward cognitive, specifically positive, reframing as a driving mechanism of outcomes following psychedelic self-medication for chronic pain and bear relevance to previously discussed change mechanisms in the context of psilocybin therapy for depression research (86). Even though many contributors reported still experiencing chronic pain following their experiences, they claimed feeling a newfound sense of agency and optimism regarding their pain. The perceived relevance of these trends further put into question the mind-body dichotomy of current pain treatments, where psychological interventions are largely considered as secondary, if at all.

Changes in perspective described by contributors were often galvanized during the acute psychedelic experience, and often persisted for 2+ months. This is consistent with existing psychedelic data suggesting transdiagnostically significant long-term outcomes in openness (115), attitude (116), personality (117), depression and anxiety (86, 118) reported for months to years (119) following treatment. PPI discussions did not include assessment of specific personality traits. Therefore, no generalizations linking specific personality or psychological traits to outcomes can be made. The acute psychedelic experiences conformed to previous findings (86) and generally centered around feelings of connection, love, compassion, and trust. As with previous studies (86, 87), these sentiments, particularly connection with the self and body, endured and precipitate the development of larger shifts in perspectives. Feelings of compassion, empowerment, and hope were closely linked and contributed to a growing sense of agency and control over their pain, and life more generally. Increased subjective acceptance of pain was also claimed, specifically shifting from a defeated resignation to an active acceptance and served as an impetus to impact other aspects of life. A noteworthy minority of contributors (5) were reportedly more committed to taking an active stance in their recovery in various ways, from seeking professional help to cultivating new behaviors conducive to general health and wellbeing [see (120)]. Overall, the subjective reclamation of identity, agency, and hope emerged as drivers in the perceived efficacy of pain management. Fostering this process has consequently developed into a central aspect of our therapeutic approach spanning the duration of the study. Reinforced integration support will aim to support the longevity of changes by providing tools for independent support and additional follow-ups.

Such outcomes are the goal of numerous treatment strategies, particularly PMPs using CBT and ACT, which aim to reframe thought processes and encourage independence. While fairly widespread, PMPs are moderately effective at best, particularly at long-term follow-ups (3942, 121). In contrast, contributors perceived a “profound shift” in perspective, which they felt contributed to the longevity of outcomes. Such claims of insight are well-supported in the psychedelic field, particularly in the context of psychological flexibility (122, 123) and further, relaxed beliefs (124) and may account for the effects reported here. Psychological flexibility facilitates well-adjusted individuals to adapt their mindset to life's ever-evolving situations, regardless of social, emotional, or stress factors (125). Existing literature points toward prodigious upregulations of neural plasticity following psychedelic experiences, translated experientially to changed perspectives (124). This is particularly relevant in populations with maladaptive, entrenched thought patterns such as depression (126), and indeed chronic pain (99). Consistent with this PPI project, therapeutically useful changes in outlook are linked to certain noetic experiences (127), allowing individuals to move “above” themselves toward a more equanimous state free of unwarranted pessimism. The cumulative results are an amalgam of self-confidence, inspiration, and acceptance (123) and directly counter the effects of pain catastrophisation.

Contributors' physical experiences of their body and pain were another point often referred to. Initially, contributors reported severe day-to-day pain, described as “burning,” “exhausting,” “looming,” “tight,” “stabbing,” and “blinding,” which left all contributors with impaired general function. Therefore, contributors were “shocked” and “in disbelief” at the perceived efficacy; 9 out of 11 contributors claimed partial or complete analgesia in the acute psychedelic stage [see (128) for similar findings]. Most contributors regained function, e.g., the ability to walk unencumbered, and described experiencing their body as “healthy.” This was reported with both high (macro) and microdoses. Effect duration varied and ranged from no relief beyond the acute experience to over a year—most contributors, regardless of dose taken, reported feeling reductions in pain for at least 3–5 days following their experience, with pain levels gradually increasing over time. Other changes were longer lasting though; most contributors (9) reported enduring increases in positive embodiment and interoception, which inspired a desire to treat the body better in the future.

The process toward pain relief often involves an improved sense of Somatic Presence, or “mindfulness of body.” Theories exist about the impact of trauma on somatic symptoms, e.g., chronic fatigue and chronic pain (129, 130). According to these theories, an act of intense physical expression/release, such as through shaking, vocalizing, or unconscious movement (also termed “somatic discharge”) can be profoundly cathartic and processing/working through associated symptoms (88, 131). Preliminary evidence suggests that somatic discharge may be effective not only for trauma therapy (132), but also in the context of chronic pain (32). Something akin to somatic discharge was described by two contributors in our group, who were interestingly also the only contributors who reported total analgesia indefinitely after their experience. The remaining contributors reported more subdued physical release, often associated with self-imposed elements of body- and breathwork. This largely resulted in muscular relaxation translating to subjective pain relief and heightened embodiment. These reports inspired the inclusion of behavioral investigations on interoception and body awareness in future studies Further, optional movement elements aimed at an embodied experience may be incorporated in dosing and integration sessions. Finally, references to potential elements of somatic discharge stimulated the development and implementation of a physical catharsis measure.

Importantly, not all contributors reported acute pain relief; three contributors reported amplified pain during the acute psychedelic experience. Pain reportedly grew in intensity and became “distressing” and “overpowering” before returning to baseline after the experience. While unpleasant, two contributors reported that this was a useful learning experience for them. One contributor branded this experience an outlier attributed to a “recklessly” high dose taken “rashly” and without proper consideration regarding attitude and intention. Other contributors echoed that taking very high doses in sub-optimal contexts (inadequate preparation, negative mental state, stressful environment) contributed to unfavorable experiences, although this did not necessary result in perceived pain amplification. We have therefore developed preparation sessions specifically tailored for chronic pain populations and will emphasize trust, transparency, and intention.

Due to the clandestine nature of illicit substance use, there is no standard protocol for self-medication. Interestingly, many contributors intentionally recreated a clinical setting in an effort to facilitate a therapeutic experience; they set specific intentions, laid back comfortably with their eyes closed, listened to especially chosen music, and focused on the internal journey, though this was largely without an accompanying “guide” or “sitter.”

Psychedelics were routinely combined with other adjunct practices. Supplementary modalities included breathwork, mindfulness, meditation, and movement, e.g., Yoga, Qi Gong, physical therapy exercises, and using expressive outlets such as art, journaling, and dance to manifest and process emotional content during and after the experience. These suggestions were incorporated into our therapeutic model with particular emphasis on mindfulness and movement.

The goal of this PPI project was not to produce formal research; it did not test hypotheses or draw any confirmatory claims. However, the most pertinent limitation of this project concerns both contributor and investigator bias. We invited collaborators through targeted advertisements which disproportionally attract people with positive experiences, causing selection bias. This was reinforced by lack of financial compensation and the time commitment of the project, ultimately resulting in a small, self-selected, and highly motivated cohort that was almost definitely biased by compelling personal outcomes. Further, recency, recall, response, and confirmation bias may have affected perceived efficacy and accuracy of reports. While we attempted to minimize researcher bias during analysis by cross-referencing for inter-coder-reliability, the inherently subjective process cannot eliminate potential confirmation bias. Equally, though discussions followed a consistent structure, unintentional interviewer bias (e.g., via body language) cannot be excluded. We reiterate therefore, that these reports are best viewed as a collection of discussions used to inform our upcoming trial and do not imply causation, generalizability of results, viability of treatment, or future study outcomes.

Beyond bias, most contributors approximated doses, challenging the accuracy of self-report quantities. Even if contributors accurately reported, there are distribution inconsistencies in both organic and synthetic materials. Additionally, evaluating the differences between microdosing and macrodosing is difficult due to potentially discrete processes (133). Duration between self-medication and discussion necessarily varied, contributing to differences in follow-up times reported and the perceived duration and efficacy of therapeutic effects. Finally, psychedelics were used in concert with other modalities, which likely confounded outcomes. If undertaken as formal research, future improvements may include more rigorous contributor selection criteria, further standardized discussion formats, and including additional cross-referencing techniques to address subjectivity concerns.​

Conclusion

In conclusion, this qualitative exploration of 11 open-ended discussions addressed perceived effects of psychedelic self-medication on aspects of chronic pain. Analysis suggested two possible processes at play during psychedelic self-medication for chronic pain: (1) Positive Reframing of contributors' relationships with their chronic pain toward perspectives of hope, empowerment, and optimism. (2) Somatic Presence fostered increased embodiment and was associated with lasting analgesia. Psychedelics were not used in isolation and were regularly combined with various other modalities including meditation, breathwork, and movement, which contributors felt impacted the success of their self-medication. Information concerning processes and complementary modalities provided useful additions to our protocol and should be considered when designing future trials.

*From the Study here :

 
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IV Ketamine safe and effective for cancer-related neuropathic pain*

by Tylar Stanley | Clinical Pain Advisor | 30 Jun 2021

According to research results published in Pain Medicine, intravenous (IV) ketamine has shown to be an effective and safe protocol for the treatment of cancer-related neuropathic pain (CNP) in patients with refractory pain control.

Previously, IV ketamine has been used to treat nononcologic neuropathic pain but has not been well studied for the treatment of CNP. In a single-centered, retrospective review, 57 consecutive patients who were diagnosed with CNP between April 2018 and May 2020 underwent an IV ketamine infusion protocol, which consisted of 192 infusions.

According to researchers, “Each patient’s pain was identified as being secondary to direct tumor compression.” The most common cancer diagnosis was breast cancer (13 patients), with nerve sheath tumors following (7 patients), and there were also 8 patients with metastases. Patients with underlying neuropathy or peripheral neuropathy prior to the onset of their CNP were excluded.

Treatment was a series of 4-hour infusion sessions. Before each session, the patient’s baseline parameters were obtained, including pain via the numeric pain rating scale, function, satisfaction, and use of analgesics. The first ketamine infusion started at 10 mg/h with a maximum titration of 25 mg/h, as tolerated.

After the initial session, all patients were eligible for a second and third infusion 1 week after the first session with an increase in the dosages each session as tolerated. Responders, or “patients who reported ≥30% reduction in pain based on NPRS or positive subjective qualifiers,” continued infusions about every 4 weeks with the maximum dose of 70 mg/h, as tolerated.

Overall, 74% of the patients were responders. While on the IV ketamine protocol, all responders reported having improvement in function and mobility. Of the 42 responders, 27% discontinued treatment due to unsatisfactory pain relief or adverse effects. 72% of the responders had pain relief for more than 3 weeks.

Due to the pandemic, 14 of the patients who were enrolled in the IV ketamine protocol could not continue treatment. With that, 13 out of the 14 patients returned to baseline pain, with each of them reporting anorexia and/or function, mobility, and mood worsening.

The majority of the adverse effects were neurological, including headache, dizziness, and somnolence. Gastrointestinal adverse events were nausea and vomiting. Cardiovascular events consisted of hypertension and tachycardia.

Results show that 64.7% of the adverse events self-resolved with changing the infusion rate or intervention. Contrary, 35.3% of adverse events resolved with the infusion rate being reduced or stopped, or the patient receiving as-needed medications. However, none of the adverse events were life-threatening or required hospitalization.

Study limitations include inconsistently used objective outcome measures, specifically neuropathic pain scales, NPRS scores, QOL, functional measures, and patient satisfaction. Though the sample size was small, it remains the largest study of IV ketamine as an adjuvant treatment for CNP to date.

“Additionally, these data demonstrate that an extended IV ketamine protocol is safe and well tolerated, with minimal adverse events and several patients who had long-term pain relief. Larger, prospective studies must be conducted to further illustrate the effects of IV ketamine on CNP and to explore the different parameters that may help prognosticate a good response to IV ketamine.”

 
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Can psychedelics treat pain?*

LSD and psilocybin increasingly show promise as mental health treatments. Now universities and companies are exploring their use in pain management.

by Troy Farah | Scientific American | 30 Sep 2021

When Kevin was just 11 months old, he was diagnosed with type 1 diabetes, which led to other health problems as he grew up: loss of vision in his left eye and peripheral neuropathy, a painful condition caused by nerve damage. Then, in 2019, a colonoscopy revealed he had colon cancer.

Feeling anxious and depressed, Kevin (a pseudonym) decided to try self-medicating with psychedelics, including psilocybin-containing “magic mushrooms.” Twice a week, the now 28-year-old delivery driver takes about half a gram of the outlawed fungi. This amounts to too little psilocybin to induce a full-blown trip, and Kevin says he quickly noticed an improvement in his mental health—a result that is in line with a handful of recent studies about the drug’s clinical potential. And he was pleasantly surprised to find that his physical pain seemed to decrease as well, even on the days he was not taking anything.

“A lot of the anxiety and depression I was dealing with started to fade away—and then the pain in my legs started to go away,” Kevin says. “I’m feeling the lasting effects from the psilocybin on my stomach and colon pretty much all the time.”

Vivid colors, warped textures and sounds, and intense introspection are famously associated with the psychedelic experience—and now, increasingly, so are improvements in mental health conditions such as anxiety and post-traumatic stress disorder. But what about pain relief? That is the question a growing number of researchers are asking, based on anecdotal reports that drugs such as LSD or psilocybin can help with this. Both drugs are currently illegal under federal law, though medical studies on them are now being officially cleared with increasing frequency.

From psychedelic start-ups to university labs, scientists are starting to test such drugs on various types of pain: cluster headaches, chronic pain, fibromyalgia and even phantom limb pain. This May a New York City–based, multimillion-dollar psychedelic start-up called Mind Medicine (MindMed) announced Project Angie—a series of studies using LSD and an undisclosed drug to treat chronic pain.

“We don't really know how psychedelics work to modulate people’s long-term symptoms in any illness, let alone pain disorders, which are less studied than some of the others,” says physician Dan Karlin, MindMed’s chief medical officer. “But there is compelling preclinical evidence that they work ... via psychological mechanisms … but also may have some direct effects on descending pain pathways.”

Tryp Therapeutics, a California-based psychedelic start-up, is exploring chronic pain relief using psilocybin and another, psilocybin-based drug with an undisclosed formulation that is obliquely called TRP-8803. The company has also partnered with the University of Michigan to study how these drugs might treat fibromyalgia, a complex and little understood condition blamed for pain throughout the body. Tryp has added leading psychedelic researcher Robin Carhart-Harris to its scientific advisory board, and the company says he will play a “critical role” in clinical trial design.

Earlier this year Yale University announced a trial using psilocybin for cluster headaches. And in August the Oxford, England–based pharmaceutical start-up Beckley Psytech raised $80 million for psychedelic research. Part of this will fund a phase 1b safety trial investigating low-dose psilocybin to treat a rare kind of headache called a short-lasting unilateral neuralgiform headache attack.

These efforts are in very early stages, and so far any results are far from clear. Some experts argue that the evidence for psychedelics relieving pain is weak and that these drugs are so powerful that they should only be used in psychotherapy—if anywhere. Even if psychedelics can relieve physical pain, they may not be better tools than those that are already widely available.

“Pain is this four-letter word that can mean so many different things,” says Vivianne Tawfik, an assistant professor of anesthesiology, perioperative and pain medicine at the Stanford University School of Medicine. At an outpatient clinic, Tawfik treats rare and refractory types of pain usually associated with surgery or injury, such as chronic neuropathic pain and complex regional pain syndrome. “There’s a role for opioids,” she says. “There might end up being a prescribed role for psychedelics. The jury’s still out.”

Tawfik warns that any off-target effects of psychedelics need to be carefully monitored. “I think abuse liability needs to be really closely considered, making sure that there aren’t unexpected psychiatric effects, certainly in populations at risk,” she says.

History of pain and psychedelics

One of the earliest recorded studies of pain relief from psychedelics was conducted by Eric Kast, an Austrian-born physician who fled the Nazis with his family in 1938 and resettled in the U.S., later becoming an anesthesiologist at Chicago’s Cook County Hospital. Kast had an early interest in how to measure pain responses: in 1962 he designed an elaborate apparatus—a pneumatically operated “mechanical pain-producing device”—that used air pressure to let a subject apply a “pain-producing element” (possibly a needle) to their own leg.

Two years later his attention was drawn to the powerful psychedelic LSD, which he tried giving to 50 “gravely ill” patients afflicted by pain with causes ranging from cancer to gangrene. They first received the synthetic opioids hydromorphone (Dilaudid) and meperidine (Demerol)—and later they were given 100 micrograms of LSD as well. This would be a strongly psychoactive dose for most people.

“When compared with LSD-25, both [other] drugs fell short in their analgesic action,” Kast wrote in 1964. It was a remarkable anecdote but barely investigated further. For decades this remained some of the best research in this area, aside from a few case studies.

“I feel like most of the studies that were done weren’t done well,” says Fadel Zeidan, a neuroscientist who studies the underlying mechanisms of pain and mindfulness at the University of California, San Diego. Zeidan, who is co-leading a study on psilocybin for phantom limb pain, would like to see “higher standards, more rigor” in this area of research. In 2020 he co-authored a review that weighed the evidence of psychedelics relieving chronic pain and proposed a mechanism of action. The review noted that psychedelics act on the body’s serotonin receptors—notably the type known as 5-HT2A—which have been linked in some research to the development of chronic pain.

“Serotonin is also involved in descending modulation of pain, from the brain down to the spinal cord,” Tawfik says. But she and others note there are currently very little data to back up the hypothesis that psychedelic pain relief acts through this mechanism. “Even though we know that some of the receptor systems that underlie pain are probably similar, there’s probably a lot of nuance that we don’t really know yet or appreciate.”

One of the few double-blind, randomized, placebo-controlled studies on this topic was published last year. Researchers at the Netherlands’ Maastricht University and their colleagues trialed 24 people who were given an oral solution of ethanol containing either a low dose of LSD (too low to cause strong effects such as visual disruptions) or a placebo. Then the subjects placed their hands in almost freezing water. The longer they could keep their hands submerged, the better their pain tolerance was determined to be.

Ratings of pain tolerance from subjects who received LSD were comparable to those in studies with the opioids oxycodone and morphine, leading the authors to conclude in the Journal of Psychopharmacology that “low doses of LSD might constitute a novel pharmacological therapy.”

Again, the researchers hypothesized that serotonin receptors had a role in this effect. Two of the scientists who conducted this study, Matthias Liechti of the University of Basel and Kim Kuypers of Maastricht University, are currently working with MindMed on its LSD and pain research. And the paper’s lead author, Johannes Ramaekers of Maastricht University, says he is developing another pain study to look at psychedelics and fibromyalgia.

But Boris Heifets, a Stanford Medicine anesthesiologist who studies pain—as well as “rapid acting psychiatric therapies,” including psychedelics—says the focus on serotonin in pain relief is probably a “red herring.” Heifets (who is beginning a trial looking at psilocybin and chronic lower back pain) argues that the fact that psychedelics can also improve mood should not be overlooked, given neurological connections between pain and depression.

“If these drugs are going to help, it’s going to be much like the way we think they help for depression—[that is], changing your relationship to your pain,” Heifets says, emphasizing that psychotherapy is the core of psychedelics’ apparent effectiveness in mental health. “The revolution with this class of medicines is that it's really not just medication alone.... This whole body of research is emphasizing the importance of therapy, psychological support and connection.”

U.C. San Diego’s Zeidan agrees. What a drug like psilocybin could be doing is helping “treat the whole person,” he says—adding that he believes this should be a greater focus of modern medicine in general.

“Chronic pain is really just this comorbid snowball of shit,” Zeidan says. “It’s not only the sensory abnormalities, but it’s also the depression, the anxiety, the sedentary lifestyle, the self-doubt, learned helplessness—it’s this whole thing.”

If psychedelics are ever prescribed for pain, it would not be the first time a drug developed for another kind of treatment has been co-opted in this way. Gabapentin and pregabalin (Lyrica) are two antiseizure drugs now commonly prescribed for nerve pain, while duloxetine (Cymbalta) is an antidepressant often used to address chronic musculoskeletal pain.

Despite the scarcity of solid evidence that psychedelics can tackle physical pain, some people like Kevin are not waiting. Three others interviewed for this article claim to use LSD to treat different types of pain, from cluster headaches to degenerative disc disease in the neck and lower back.

All say they are willing to risk breaking the law because they have tried everything else, with very little success. The steadily increasing research could shed some light on whether these long-demonized drugs can relieve physical suffering—or if they are simply placebos—while also examining long-term side effects.

“Every individual’s experience of chronic pain is unique,” Tawfik says. “Many of my patients are still looking for better treatment options.... We just always need to have these risk-benefit conversations with any of these medications.”

*From the article here :
 
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Cannabis Oil for Pain Management: Does it Work?

by Amber Kraus & Dr. David Cox, PhD, ABPP | Psychable

Cannabis oil is a product that is made by extracting the cannabinoids (such as THC or CBD) from cannabis buds and flowers. Recently, CBD products have gained popularity as a treatment for a number of ailments. CBD products that contain little to no THC are popular because they are legal in most states and provide pain relief benefits without the psychoactive properties of THC.

What is cannabis oil?

CBD and THC are the main active substances in cannabis plants. Cannabis oil contains one or both of these substances. The oil is extracted from a cannabis plant and then usually mixed with a carrier oil.

Cannabis oil can be consumed orally by placing a dropper under the tongue. It can also be used topically in the form of creams or lotions, to be used on skin problems such as eczema and psoriasis. Some people will also rub topical cream on sore muscles or joints to help with pain relief. Soft-gel capsules containing CBD oil (but not THC) are also becoming more popular and are sometimes mixed in with other supplements like probiotics.

There are several different types of cannabis oil:​
  • Isolate: contains only CBD and has no other cannabinoids. This oil contains no THC and has no psychoactive properties.​
  • Full-spectrum: contains all cannabinoids that are found naturally in cannabis plants, including CBD and THC. Full-spectrum CBD oil is only legal in some states.​
  • Broad-spectrum: contains multiple cannabinoids but does not contain THC.​
  • THC oil: contains mostly THC and therefore results in a person feeling “high”. THC oil sometimes also contains CBD.​
Is CBD oil legal?

The laws around all cannabis products are complicated and vary by state.

CBD oil that does not contain THC or that contains less than 0.3% THC was made legal by the federal government in 2018 when President Trump signed the Agricultural Improvement Act of 2018, also known as the 2018 Farm Bill. This law removed hemp from the Controlled Substances Act, which allows CBD products made from hemp to be sold legally.

Although CBD oil is federally legal, state laws vary and can be complicated. You can find information on CBD laws in your state here.

Cannabis oil that contains THC is still illegal in most states, although many states are moving to legalize THC either for medical or recreational purposes.

Can cannabis oil help with pain management?

CBD and THC trigger the body’s cannabinoid receptors with different effects on brain chemistry which can cause certain mental or physical reactions. The high that a person gets from THC has been associated with improved pain-relief because it blocks the pain signals being transmitted to your brain. THC is sometimes used by cancer patients to reduce pain and nausea. However, for most people, walking around feeling high all day isn’t a reasonable solution to chronic pain, which is why some people choose to use CBD oil for pain management.

CBD oil doesn’t make a person feel high, but early clinical evidence suggests that CBD offers therapeutic benefits in some people and can provide pain relief in certain conditions, which may improve people’s quality of life. It has the potential to help with inflammation caused by certain autoimmune disorders, infections, or illnesses. Studies in animals show that CBD can help with pain. Evidence in animal studies showed that CBD oil works by interacting with the endocannabinoid system, the inflammation system, and pain sensing systems in the body. While the early research that has been done shows promising results, more research still needs to be done on human subjects.

Some people have reported that CBD oil can help improve sleep. For people who struggle with chronic pain this can be a major benefit, as their pain often keeps them from getting a good night’s sleep, which can result in even more complications such as brain fog and a weakened immune system.

Are there risks to taking CBD oil?

CBD can cause mild side effects like nausea, fatigue and irritability. There are no reported serious side effects with CBD products, although they can cause your blood to thin, which may be dangerous for some people.

Because CBD is considered a supplement and not a medication, there is no governmental regulation of CBD products, which means that purchasing them in a store can come with some risks. If not purchased from a reputable source, you run the risk of either purchasing a CBD product that is mixed with other chemicals, or a product that is not high-quality. Purchasing a CBD product that is mixed with other substances can be dangerous if you don’t know what’s in it. The biggest risk of purchasing a low-quality product is wasting money on something that isn’t what is being advertised.

The Bottom Line

Like many other psychoactive substances, the research on cannabis is ongoing. And while anecdotal reports from individuals and surveys suggest that CBD and THC can help with pain caused by chronic or acute inflammation, there is not enough research to definitively link the two. Where CBD and THC products are legal, it is ultimately up to the consumer to research the product and weigh the risks and benefits of use. If you are suffering from chronic pain or a chronic illness, you should consult your doctor or other health provider to see if cannabis oil might be a promising solution for you.

 
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Are Psychedelics the Future of Pain Relief?

Some scientists believe that LSD and psilocybin could treat everything from cluster headaches to fibromyalgia.

by Mattha Busby | VICE | 9 Feb 2022

For more than 15 years, Ainslie Course suffered from one of the most intense pains known to humans: cluster headaches. Sometimes nicknamed "suicide headaches", her main symptom was an excruciating pain that suddenly surrounded one eye in debilitating bouts of attacks. These cycles could last for months, and acute sufferers are known to be statistically more likely to take their own lives. But none of the traditional treatment options worked for Course. Instead, psychedelics were her saviour.

“My experiences with psilocybin therapy were life-saving,” says 55-year-old Course, now the vice-president of a non-profit organisation called Clusterbusters. “Not only did psilocybin help to control the acute nature of the attacks, but it greatly lengthened remission times between cycles." On pharmaceutical medicines, she would rarely be migraine free for a few months. "But with psilocybin, my remission periods are up to two years.”

In fact, it increasingly seems that pain – one of the most universal experiences in the human condition – is now the next frontier for psychedelics after mental health. And the use of psilocybin to ease cluster headaches is not the only line of investigation. LSD is now being investigated by startups and universities around the world for its treatment of chronic pain and fibromyalgia (a debilitating condition which causes, among many other symptoms, excruciating stiffness).

High quality evidence remains scarce, but dozens of emerging trials go some way towards validating widespread anecdotal reports that psychedelics can play this role. “There’s a case for cautious optimism and continuing to push the cause,” says James Close, a doctoral student at the Centre for Psychedelic Research at Imperial College London and pain management therapist at Imperial College Healthcare NHS Trust.

Early and preclinical evidence suggests that psychedelics might have a positive effect on the psychological mechanisms and neural pathways associated with persistent pain. “Looking at the depression and PTSD studies, you can see quite conceivably how psychedelics might help people change the relationship they have with their chronic pain,” says Close.

Why is that so? A key advantage of psychedelics over prescribed drugs is that they can work holistically to free the brain from deep-rooted habits, thus opening people to new states of mind. Among those experiencing serious and persistent pain due to resistance in the brain to change, "psychedelics could create plasticity and, so to speak, allow for the slate to be wiped clean," says Close.

Later this year, the results will be published from the world’s first early stage trial into the efficacy of psilocybin in rare headache attacks, conducted by the British firm Beckley Psytech (set up by Lady Amanda Feilding). Elsewhere, a Maastricht university study in 2020 announced that very low doses of LSD could be as effective as opioids for pain relief.

“LSD has such a prolonged effect that if you took a low dose in the morning you could be somewhat protected all day, whereas people have to redose opioids several times throughout the day – and there is also the potential for dependency and far greater scope for abuse,” Dr Jan Ramaekers – who led the research – told VICE. “Low doses of psychedelics do not induce psychoactive effects and therefore provide a practical way to use psychedelics as analgesics[pain relief.”

Psychedelics for pain have long shown potential. As far back as the 60s, clinical trials were discovered the profound pain relief that could be offered by LSD, but when President Richard Nixon’s war on drugs began in 1971, it soon halted all subsequent research and studies into the benefits of psychedelics. Only now is it being taken seriously again. And while hospital data from patients is still absent, the literature is growing. Companies are now making patent claims on psychedelics as medication for pain, such as a type of MDMA for care following surgery.

“Psychedelic substances have a generally favourable safety profile, especially when compared with opioid analgesics,” reads a review paper in a 2020 British Medical Journal publication. Another paper published in December noted that clinical observations over the past decade suggest "psychedelics may possess heuristic value for understanding and treating chronic pain conditions”.

One of its co-authors, Amanda Pustilnik, a neuroscience law expert from the University of Maryland, told VICE: "There are numerous mechanisms in psychedelic drugs, particularly psilocybin, but possibly others, that could potentially affect chronic pain disorders. Their potential could be tremendous."

Ketamine, arguably a psychedelic, is being prescribed privately in the US and UK for depression, and has been shown to dramatically reorganise pain pathways. "The domains of pain, anxiety and depression are all connected,” adds fellow co-author Dr David Borsook, a director of the pain and imaging neuroscience group at Massachusetts general hospital. “If you treat one, another often gets better.”

There is an urgent need for effective, non-addictive medications for chronic pain, adds Borsook, who also works as an advisor to a company commercialising psychedelic-based therapies. However, he says, “the opportunities need to be channeled into robust studies.”

Criticism over the pace of research and the bureaucracy around psychedelic experiments is growing, with psilocybin and LSD studies facing serious hurdles in many places across the world, including the US and UK. "But if you look at the number of articles being produced and the amount of academic centres committing to research in this domain, steps are being taken in the right direction," says Borsook.

The demand for pain medication in the UK has been rising rapidly, mirroring trends in the US. There has been a steep increase in prescription for pregabalin and gabapentin pills, which are class C drugs due to their high strengths and addictiveness. “Chronic pain is the greatest clinical problem in the UK behind depression,” adds Close. “The response rate to the current treatments is very low.”

Some observers have described this rise in pain, and the absence of an effective treatment, as the collateral damage of the war on drugs, thanks to the politically-motivated prevention of research and enforced scientific dormancy. And the US opioid crisis is a stark example of these warped priorities. It has resulted in tens of thousands of deaths – partly due to institutional medical negligence driven by profit – when potentially better treatments may have otherwise been made available.

“There was a concerted strategy on the part of certain bad actors to promote these drugs to individuals who didn't have the right medical indication for them as a business strategy to create addiction,” says Pustilnik.

Pressure is growing on health authorities to rapidly fund research and sanction the treatments through exemptions – such as in Canada – while the British prime minister has faced high-profile calls from within his Tory party to downgrade psilocybin from the strictest scheduling in order to reduce barriers to research.

“I tried dozens of medications including blood pressure pills, strong painkillers, oral steroids in huge doses and nerve blocks into the back of my head. But rather than properly treat me, I gained weight, was sleepless, agitated, got kidney stones, experienced cognitive fog and memory issues, plus my bones thinned and my joints became weak,” says Course, one of thousands of people to have used psilocybin to treat their pain."

“I find it very difficult to accept that psilocybin is classed as a schedule one drug, which we are told has no medical or therapeutic properties.”


 
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Using Psychedelics to Treat Chronic Pain

Psilocybin is a psychedelic, and the active compound in "magic mushrooms". Recent research has demonstrated potential for using psilocybin—which is not habit forming—for treating some mental health disorders. But it hasn't been well studied for use in treating chronic pain. Here's what happened when one chronic pain patient used it for his neuropathy.

by Rosemary Black | Practical Pain Management

Every day, William Jones (*name changed to protect privacy) puts some psilocybin mushrooms into a coffee grinder, grinds them until they are fine, and transfers them to gel capsules. He swallows the capsules with a sip of water, and within 20 to 30 minutes, he feels relief from the pain that has followed him since he was diagnosed with autoimmune peripheral neuropathy in 2005.

“The pain in my feet was frequently very severe, debilitating, and chronic,” Jones recalls. “I saw many specialists and used many prescription drugs and experienced little or no pain relief.”

Within 20 to 30 minutes after consuming the psilocybin capsules, however, he gets relief.

“I have consistently had pain-free evenings for the first time in many years once I decided to try what I call mushroom therapy,” says Jones, 69, who lives in Colorado. “I feel this could be an option for patients who have treatment-resistant chronic pain.”

Jones decided to try them after listening to a podcast about the potential of psychedelic drugs to relieve addiction, anxiety and depression. “I decided to try psilocybin mushrooms after I read about the use of psychedelics to treat psychological disorders,” he recalls. “I learned that there was often great success compared to prescription drugs and interventional treatments.”

Psychedelics: Limited Research for Chronic Pain Conditions

There has been some interest in the use of psychedelics like psilocybin and MDMA (aka, ecstasy or molly) for treating mental health conditions like depression, anxiety, and PTSD. So far, the research is scant on how these drugs work to lessen chronic pain.1

But even though the evidence for using these drugs to treat chronic pain is limited, some studies have demonstrated potential benefits for cancer pain, cluster headache, and phantom limb pain.

One study found that individuals with migraine who took psilocybin reported fewer migraines during the test period than those who took a placebo. The people in the study kept headache diaries and at the end of the testing period, those who had received the psilocybin reported a “significant” reduction in their migraine.2

“This exploratory study suggests there is an enduring therapeutic effect in migraine headache after a single administration of psilocybin,” wrote the study authors.2

At the University of California San Francisco, a study will look at whether psilocybin therapy is effective for people with chronic low back pain.

“This study examines the effects of a single dose of psilocybin in combination with therapeutic preparation and integration studies,” the university notes. “We hope psilocybin therapy will lead to improvements in pain interference…related to chronic back pain.”

Marc Perez, MSN, MHA, MBA, is a psychiatric nurse practitioner resident in the San Francisco VA Health Care System. He says the research on the use of psychedelic drugs to treat chronic pain is not widespread yet. “It is not getting much traction, although I feel that it is worth investigating,” he says.

How Psychedelics Work

Psychedelic drugs increase neuroplasticity, which is linked to mood, optimism, and a rewiring of the brain, says Mike Dow, PhD, PsyD, of Field Trip Health, a California-based provider of psychedelic therapies.

According to research conducted by David Nichols, PhD, psychedelics are powerful psychoactive substances that alter perception and mood and affect numerous cognitive processes. They are generally considered safe and do not lead to dependence or addiction.5

Yet since 1970, psilocybin has been classified as a Schedule 1 illicit drug, which is defined as having no currently accepted medical use in the US, as well as a high potential for abuse. Hundreds of different compounds are classified as psychedelics or hallucinogens, including well-known drugs like LSD, magic mushrooms, peyote, and ketamine, according to related information availlable on the American Addiction Centers website.

How psychedelics work to alleviate symptoms long term in any illness isn't known and hasn't been well studied—especially for chronic pain—but Dow says he is hopeful forthcoming research will study the use of psychedelics for chronic pain. “I am hopeful that future research will lead us to the right combination of drugs that are helpful to those in pain,” he says.

Stephen Thorp, MD, an interventional pain medicine expert at Northwell Health who is board-certified in anesthesiology and pain medicine, doesn’t rule out the use of psychedelic drugs for chronic pain. “We just aren’t there yet,” he says. “While there is some promising data, there are no hard clinical outcomes yet.”

Pain Management with Psilocybin: A Few Pain-Free Hours

Jones says that his dose of psilocybin mushrooms doesn’t cause any cognitive impairment or reality distortion. “The doses are effective for three to five hours and there have been no adverse side effects or hangovers,” he says. “I feel pleasant, mentally sharp, and pain-free. There are no side effects.”

He does experience some breakthrough pain, he says. Typically, his pain waxes and wanes in the afternoon, staying at around 3 to 5 on a pain scale of 1 to 10. It tends to spike to 7 or 8 in the evening. But the last year has seen an improvement, thanks to his psilocybin mushroom treatment. “Still, it is a lot of trial and error,” he says.

Dr. Thorp feels that research in the area of treating chronic pain with psychedelics is important. “More than 20% of the population is in chronic pain,” he says. “We need more tools in the toolbox to treat them.”

The Physical and Mental Health Effects of Psychedelics

Psychological distress such as disturbing hallucinations that can last for a few days, is the most commonly-reported adverse affect of using psilocybin. Factors such as your mood, the dose, who you are with, and your current mental state can impact the experience and exacerbate or trigger the onset of underlying psychotic conditions.

Michael McGee, MD, staff psychiatrist at Atascadero State Hospital in California and author of The Joy of Recovery says people with a personal or family history of conditions like schizophrenia are at high risk of long-lasting harm and should avoid psilocybin.

"Psilocybin is a powerful tool that can be harmful if used in a dangerous way," Dr. McGee explains. "So, it's best to use them only in a research setting. Remember, these drugs are illegal except for research purposes."

Chronic use of psilocybin also comes with cardiovascular risks, as well.6

It binds to HT2B receptors, which can cause dangerous changes in the structure and shape of heart valves. (Fen-phen—another drug that binds to HT2B receptors—was pulled from the market due to risk of valvular heart disease, one cause of heart failure.)

It's worth noting, however, that experts believe this likely isn’t an issue when you’re taking the drug once or a few times for therapeutic effect.

 
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Can psychedelics treat chronic pain?*

by Suzannah Weiss | DoubleBlind | 14 Sep 2020

From ayahuasca to iboga, and even synthetic compounds, people are turning to psychedelics to treat pain, in addition to mental health.

During the first year I spent suffering from chronic Lyme disease, I tried all kinds of treatments, including antibiotics and other Western medications, along with alternative methods like acupuncture, herbal supplements, ozone, and hyperbaric oxygen therapy—but they only took me so far. Still experiencing insomnia, heart palpitations, headaches, fatigue, bladder irritation, and muscle twitches, I took several friends’ recommendation to undergo a ceremony with iboga, a powerful psychedelic made of the African tabernanthe iboga plant.

After my first iboga ceremony with a shaman in Mexico, I was shocked that not only did my Lyme symptoms completely lift, but the pain that I’d been feeling in my knees after falling on them a month prior was also gone. The Lyme-related issues returned after a few weeks, but the more I did iboga—six times total over the course of that year—the more and more lasting the effects were, and the better my knees got as well.

I’m not the only one to experience a physical transformation like this through psychedelics. Michael Mationschek, a healer in Mallorca, Spain who works with psychedelics, says iboga completely repaired neurological damage he’d incurred after an accident.

“It was so bad that I couldn’t feel half my face, memory didn’t work, couldn’t walk straight, life force was cutting out,” he says. “And iboga saved my life. The first journey I did with iboga, my motor neocortex rebuilt itself. The next morning, I was eating breakfast and I could see my hand recalibrating itself as if I was using it for the first time. And I could feel my face again and started to get some memory functions back.”

It’s not just iboga that can heal physical ailments. Maria Johanna, who used to run ayahuasca retreats in the Netherlands, has worked with multiple people who saw relief from physical complaints. One woman who could not move her feet walked for the first time in ages after participating in one of her ceremonies.
“The first journey I did with iboga, my motor neocortex rebuilt itself. The next morning, I was eating breakfast and I could see my hand recalibrating itself as if I was using it for the first time.”

Nor is it only natural psychedelics within the “plant medicine” category that can work wonders on physical ailments. Jen, a 47-year-old in the Chicago area, noticed improvement in her chronic migraines after an acid trip. “It seemed to help both mood and migraines for about three weeks,” she says. The nausea associated with her migraines was completely gone for those three weeks, and she also had more energy. Caitlin Thompson, founder of the mental wellness supplement company EntheoZen, says LSD helped her manage chronic nerve and joint pain, while also alleviating her pain for weeks after each trip.

Psychedelics have been investigated over the past few years for their ability to help with various mental health conditions, including anxiety, depression, and PTSD. What’s less well-established—but equally promising—is their potential to help people heal from physical health conditions.

Johanna believes such transformations are possible because ayahuasca and other psychedelics heal the emotions, which are connected to the body. Some fields such as somatic therapy contend that emotions from past experiences can get trapped in the body, causing pain and other symptoms, and research has correlated traumatic childhood events with physical illnesses. “I believe in the holistic principle—everything is connected, so if you have illnesses or if your body is giving signs, it means something,” says Johanna. “Changing the inner world is changing the outer world.”

James Giordano, professor of neurology and biochemistry at Georgetown University Medical Center, agrees that psychedelics can influence the body through the mind. “It’s important to consider the role that neurological systems—including the brain—play in integrating and regulating our physiology, as well as our thoughts, feelings, and behaviors,” he says. “These functions are not mutually exclusive, but instead can be—and often are—dynamically interactive.”

"Sometimes, psychedelics improve people’s health by inspiring them to change their behaviors,"
says Johanna. “One thing that happens so many times after ayahuasca is that people don’t want to drink alcohol or eat meat anymore because it shows you how important your health is, and you’re more connected with your body,” she says.

Psychedelics can also increase awareness of what’s happening inside someone’s body. Raven Marie, assistant facilitator at the iboga retreat center Awaken Your Soul, was actually able to diagnose a physical health problem because of iboga. During the ceremony, she took a journey into her body and noticed a tumor in her abdomen. This led her to get an ultrasound, and the doctor found that she had uterine fibroid tumors.

Despite the doctor recommending surgery, Marie chose to continue using plant medicine, including iboga and 5-MeO-DMT, along with other natural healing methods. During the DMT ceremony, she says she remembers feeling as if she shed the sexual trauma of her ancestors. After three months, she went back to the doctor and found out the fibroids had shrunk to the point that surgery was unnecessary.
During the ceremony, she took a journey into her body and noticed a tumor in her abdomen. This led her to get an ultrasound, and the doctor found that she had uterine fibroid tumors.

"There also may be direct physical changes that psychedelics can cause in the body. This is easiest to explain for issues like migraines or Lyme disease that involve the nervous system," says Giordano. "Psychedelics like LSD, iboga, and 5-MeO-DMT act on the serotonin system, which could allow them to alleviate a number of neurological issues. The serotonin system also plays a role in the immune system, so stimulating it could stimulate self-healing," Giordano adds. London life science company Eleusis is even working on a drug that could combat inflammation, Alzheimer’s, and retinal disease by binding to serotonin in a similar way to mescaline. In addition, the feeling of connection one might gain from psychedelics can put the nervous system in a parasympathetic state, decreasing inflammation and facilitating healing.

Iboga in particular also acts on the opioid system, which can help with pain relief, even after the drug wears off. “Injury-induced pain — like that from falling on your knees — involves a cyclic mechanism of inflammation, which triggers pain that triggers more inflammation,” says Giordano. “By blocking the pain component through activation of the opioid system, you interrupt the inflammatory-pain cycle,and ‘break the chain’ of pain perpetuation. Not only that, but substances like iboga and 5 MEO DMT might affect hormones like progesterone and estrogen, which could help with issues like fibroids."

There has not been a ton of research on psychedelics’ effects on the body, but the data that does exist is promising. One study in the International Review of Psychiatry found that activating serotonin receptors in animals in a way that mimicked psychedelics produced anti-inflammatory effects. Another in Frontiers in Pharmacology showed that iboga modifies expression of genes affecting brain regions involved in neurodegenerative disorders like Parkinson’s Disease. And ayahuasca acts on the brain’s sigma-1 receptor, which could allow it to fight inflammation and oxidative stress.

Since most potential health benefits of psychedelics haven’t been formally studied, it’s difficult to say they definitely help with certain ailments, rather than simply promoting a feeling of well-being. "However, if it’s just the latter, that’s still something," Giordano points out. “Even if the individuals reporting these results simply felt better—and felt better for a protracted, durable time after their psychedelic experience,” he says, “that in and of itself would warrant further research.”

*From the article here :
 
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Cannabis flower is most effective for pain relief, study finds

by Kimberly Lawson | August 21, 2019

Among the overwhelming variety of cannabis products available on the market today, the most effective for pain relief appears to be whole dried marijuana flower and products high in THC, a new study finds.

“Whole cannabis flower was associated with greater pain relief than were other types of products, and higher tetrahydrocannabinol (THC) levels were the strongest predictors of analgesia and side effects prevalence across the five pain categories,” researchers from the University of New Mexico wrote. “In contrast, cannabidiol (CBD) levels generally were not associated with pain relief except for a negative association between CBD and relief from gastrointestinal and non-specified pain.”

Using data from a mobile app that aims to educate users about cannabis products and help them track their experiences, the researchers found that most people who reported self-medicating with marijuana have short-term, yet significant, relief from pain. “In our sample,” they write, “we observed an average pain reduction of roughly 3 points on a standard 0 to 10 visual analogue pain scale, consistent with its application as a mid-level analgesic.”

The findings, published in Complementary Therapies in Medicine in late July, are the latest in a robust body of scientific literature that shows marijuana can help people with different kinds of pain.

The study’s goal was to gauge how the severity of pain changed and what side effects were experienced after cannabis consumption, and whether these effects differed by product. Researchers used information gleaned from Releaf App, a mobile software program developed by three of the study’s authors and released in 2016. The app allows users to monitor their symptoms before, during and after consuming cannabis, thus helping them to understand the differences between products and delivery methods.

The study—which calls the Releaf data set “the largest database of real-time cannabis administration sessions in the U.S”—analyzed 20,513 cannabis sessions recorded in the app by 2,987 people between June 6, 2016 and October 24, 2018.

“Perhaps the most surprising result,” lead author Xiaoxue Li said in a statement, “is just how widespread relief was with symptom relief reported in about 95 percent of cannabis administration sessions and across a wide variety of different types of pain.”

On average, users reported their starting pain to be 5.87 on a scale of 1 to 10. After consuming marijuana, that number fell to 2.77—a decrease of 3.1 points.

“Among the limited number of product characteristics that are typically made available to consumers, we found that consumption of whole, natural Cannabis flower was associated with greater anesthetic potential than were most other types of products,” the authors wrote.

The study also found:

- Patients whose cannabis sessions involved flower reported similar pain relief as those using concentrates and topicals. Edibles, pills and tinctures, however, offered less relief than flower.
- Concentrates were found to be associated with more negative side effects, which the researchers reasoned could be because of solvents and other additives, as well as the removal of most terpenoids, terpenes and flavonoids.
- Products labeled as hybrid strains were more effective at relieving pain than those labeled indica or sativa.
- Combustion method didn’t affect pain.
- Higher THC levels offered more pain relief, while higher CBD levels did not.
- Patients with back, joint or muscle pain, headache or migraine and non-specified pain saw more relief with high-THC products.
- Patients with gastrointestinal/abdominal-related pain found more relief with lower levels of THC.

As for other reactions, patients were more likely to report positive effects than negative effects: they cited dry mouth and feeling foggy as the most common negative ones, while feeling relaxed and peaceful were frequently reported as the most positive ones. Additionally, while CBD levels didn’t impact pain much, the cannabinoid did appear to decrease the likelihood of having negative side effects.

“The current findings,” the study concludes, “show that self-directed medical cannabis treatment, especially among users of higher THC products, is associated with significant improvements in at least short-term pain relief, perhaps a major reason why cannabis has become one of the most widely used medications in the United States.”

In a statement, Jacob Vigil, another study author and UNM associate professor of psychology, said the reason why dried cannabis flower may be more effective for pain is because of its “numerous constituents that possess analgesic properties beyond THC, including terpenes and flavonoids.” These compounds probably work together to increase cannabis’ therapeutic effects, he said.

“Our results confirm that cannabis use is a relatively safe and effective medication for alleviating pain, and that is the most important message to learn from our results,” Vigil continued. “It can only benefit the public for people to be able to responsibly weigh the true risks and benefits of their pain medication choices.”

 
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