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Psychedelics for Pain

The terms “psychedelics” and “chronic pain” do not ordinarily coexist in the same sentence. Historically, classic psychedelic compounds like psilocybin (the psychoactive ingredient in so-called “magic mushrooms”), lysergic acid diethylamide (LSD), and mescaline have been associated with everything from the counterculture of the 1960s and brain-scrambling “bad trips,” to life-changing, mystical-type experiences and unprecedented therapeutic power.

Of course, anybody who knows anything about the physiological effects of drugs knows that psychedelics, relative to other recreational substances, are incredibly safe, and do not, contrary to popular belief, scramble one’s brain or show dependence liability. Nor do they cause any of the other falsehoods of tragedy peddled in the past by poor-faith actors.

Quite the opposite, in fact.

The present psychedelic renaissance that we are all lucky enough to be witnessing has produced a plethora of meticulously conducted studies demonstrating that psychedelics can reliably occasion mystical-type experiences, and do have far-reaching therapeutic potential.

In recent years, psychedelics have shown clinical efficacy for several mental health conditions, including treatment-resistant depression, anxiety related to life-threatening illness, post-traumatic stress disorder (PTSD), and substance use disorders, prompting the US Food and Drug Administration to designate psilocybin- and MDMA-assisted psychotherapy as breakthrough therapies for treatment-resistant depression and PTSD, respectively. 

So, what about physical health conditions, like chronic pain? According to the CDC, over 50 million Americans suffered from chronic pain in 2016, approximately 10 million of which are living with high-impact chronic pain that negatively affects many aspects of their lives. Could psychedelics offer the kind of robust relief so desperately sought after, that conventional analgesic agents, such as opioids, largely fail to produce?

Treating Pain with Psychedelics: Previous Research 


The little evidence that exists of psychedelics’ pain-relieving efficacy suggests that these compounds, in conjunction with expertly delivered supportive psychotherapy, may have the potential to treat a variety of chronic pain conditions, including cancer pain, cluster headaches, migraine, and even phantom-limb pain — a rather peculiar pain condition in which constant pain is perceived as coming from a limb that has been amputated. 

Below, we take a deep dive into preliminary evidence from small-scale pilot studies, surveys, questionnaires, and case reports suggestive of psychedelics’ powerful analgesic effects. 

Treating Cancer Pain with LSD


In 1954, physician Dr. Eric Kast and his colleague, author of Principles of anesthesiology, Dr. Vincent Collins, compared the analgesic action of LSD with meperidine (Demerol) and hydromorphone (Dilaudid), two opioid medications used to treat moderate to severe pain.

In double-blind fashion, the researchers first administered either hydromorphone or meperidine to 50 sickly cancer patients, before administering whichever drug participants had not received approximately 6 hours later. At least 6 hours subsequent to administration of the second opioid, participants were given 100 micrograms of LSD. 

According to the researchers, hydromorphone was observed to exhibit more effective analgesic action than meperidine with fewer side effects. LSD, however, was observed to impressively outperform both opioids, inducing profound, enduring pain relief that remained for up to 3 weeks. According to the researchers, “patients displayed a peculiar disregard for the gravity of their situations, and talked freely about their impending death with an affect most beneficial to their own psychic states.”

Not only did LSD allow these people stricken with terminal illness to open up and consciously contemplate the altogether unfair and terrifying premature termination of their physical existence, but it produced within them pleasant sensations the beautiful intensity of which they felt compelled to describe glowingly, and the likes of which they had hitherto never experienced. 

In addition to Cast and Collins’ publication, two subsequent studies explored LSD’s analgesic action in cancer patients suffering from comorbid chronic pain. The first, a 1969 trial in which the foremost expert on psychedelic therapy, Bill Richards, was involved, also demonstrated significant pain reductions.

Following on from this, in 1973, Richards was again involved as Dr. Stanislav Grof, of Holotropic Breathwork notoriety, led a study in which LSD-assisted psychotherapy was observed to reduce pain severity, preoccupation with pain, and physical suffering in terminally ill cancer patients.

Psychedelics for Cluster Headache 


Cluster headache is a rare, treatment-resistant, chronic pain condition characterized by excruciatingly painful paroxysms on one side of the head, usually concentrated around the eye.

Sadly, current treatments, which include oxygen, sumatriptan, verapamil, lithium, corticosteroids, and other neuromodulators, fail to provide adequate relief in those unfortunate enough to be afflicted with this idiopathic neurological disorder, widely considered to be the most painful of headache types.

However, several case series and qualitative studies suggest that psychedelic substances, LSD and psilocybe mushrooms, in particular, may offer a glimmer of hope in what is an otherwise gloomy prognosis. 

After being contacted by a man who, through repeated administrations of LSD and psilocybe mushrooms, achieved complete remission of his cluster periods, which, he claimed, returned upon stopping, an intrigued group of researchers began to investigate. To do so, they interviewed a cohort of patients who met the International Classification of Headache Disorders-2 criteria for cluster headache, had received a diagnosis of cluster headache by a medical doctor, and reported the use of psilocybin-containing mushrooms or LSD to treat their cluster headache.

Interestingly, data analysis found that magic mushrooms were effective in terminating cluster attacks, aborting cluster attacks (ending attacks within 20 minutes), decreasing the intensity or frequency of attacks, and extending remission periods. 

Amazingly, LSD was reported to terminate cluster periods, something which, at least at the time of publication, had never before been observed with any other medication. LSD was also reported to extend remission periods, and produce long-lasting attack-free periods in chronic cluster headache patients. 

In 2015, assistant professor of neurology and psychedelic researcher at Yale School of Medicine, Emmanuelle Schindler, published the results of a survey that also investigated the phenomenology of self-medicating cluster headache with psychedelics and other drug types. Again, according to survey respondents:

- Psilocybin was an effective abortive treatment
- Psilocybin was an effective prophylactic
- Psilocybin and LSD provided meaningful protection against attacks in over 70% of participants
- Psilocybin and LSD prevented the onset of cluster headache in 40% of participants

Among the co-authors of this study were members of Clusterbusters, Inc., a non-profit organization dedicated to supporting research for better treatments and a cure for cluster headache. 

Psychedelics for Migraine


Approximately 10% of the global population is burdened by migraine, a recurring neurological disorder characterized by moderate to severe throbbing pain typically felt on one side of the head. Migraine can be so debilitating that 9 out of 10 people report not being able to work or go to school while suffering from an attack.

A lack of effective treatments for migraine and consequential, oftentimes risky desperation has forced treatment-resistant patients to explore alternative treatments online. To better understand the use of unapproved, alternative migraine treatments, researchers at Karlstad University in Sweden conducted a thematic analysis of personal accounts of the use of psychedelics presented in the online forum boards shroomery, bluelight.org, and clusterbusters

Martin Andersson and colleagues found that psilocybin-containing mushrooms, LSD, and related psychedelic tryptamines were effective as prophylactics and acute treatments — reducing the intensity of migraine pain and the frequency with which migraines occurred. The forum discussions largely revolved around harm reduction practices and maximizing analgesic effectiveness. 

In 2021, Schindler and colleagues conducted the first-ever placebo-controlled trial to investigate psilocybin’s potential as a migraine treatment. In this first-of-its-kind study, each participant acted as his or her own control, first receiving an oral placebo capsule, before receiving an identically appearing oral psilocybin capsule (0.143 mg/kg) 2 weeks later. Psilocybin produced:

- Significantly greater reductions in migraine frequency
- Significantly greater reductions in weekly migraine attacks
- Significantly greater reductions in pain severity
- Significantly greater reductions in attack-related functional impairment
- Significantly greater reductions in weekly migraine abortive days

Interestingly, this study did not find a correlation between the psychedelic effects of psilocybin and positive outcomes, suggesting that its analgesic action in migraine may be independent of acute changes in sensation and perception. This observation is consistent with the results of survey studies demonstrating the effectiveness of sub-psychedelic doses of psychedelics and the apparent efficacy of the non-psychedelic lysergic acid derivative, 2-Bromo-LSD (BOL-148), synthesized by legendary chemist Albert Hofmann.

Magic Mushrooms and Phantom Limb Pain


Phantom limb pain is a rather counterintuitive chronic pain condition that occurs in around 80% of amputees in which pain is felt to be coming from a part of the body that is no longer there. Experts surmise that phantom limb pain may be a consequence of miscommunication between the spinal cord and the brain caused by the survival of peripheral nerve connections despite amputation. 

As is the case with most chronic pain conditions, existing pharmacotherapies provide little to no relief, whereas alternative treatment options that send electrical impulses directly into the nervous system, can be uncomfortably invasive. These treatments too provide mere negligible, short-lasting relief in most patients. 

A 2018 case report authored by distinguished professor and neuroscientist Dr. Ramachandran and UC San Diego colleagues suggests that psilocybin may be an effective adjunct to mirror visual feedback (MVF), a non-invasive, neurorehabilitation technique first proposed in the 1990s that is used to alleviate phantom limb pain. 

The researcher's report describes the compelling story of  National Geographic explorer, Albert Lin, whose leg was crushed in a major off-road vehicle accident and required amputation from the knee down. Dissatisfied and frustrated with the ineffectiveness of conventional pain medications, Lin decided to experiment with magic mushrooms, with the fleshy fungi very much living up to its name. 

Amazingly, yet, perhaps unsurprisingly to those experienced users of psychedelics to treat pain, a single dose of magic mushrooms produced robust and lasting pain relief, which prompted Lin to try combining psilocybin and MVF.

Initially, this combination of psilocybin and MVF produced a 50% reduction in pain that lasted 3 weeks and eventually led to remission.

The authors suggest that psilocybin may enhance the effectiveness of MVF by upregulating functional connectivity between the visual cortex and the somatosensory cortex responsible for processing somatic sensations. Psilocybin’s promotion of neuroplasticity via 5-HT2A receptor agonism may enhance the brain’s receptivity to MVF, therefore improving its efficacy. 

Investigating Self-Medication of Chronic Pain 


In 2021, Ph.D. candidate at Imperial College London Julia Borneman led a qualitative investigation in which 11 people were interviewed about their experience of self-medicating chronic pain with psilocybin-containing mushrooms and truffles, LSD, DMT, and ayahuasca. Study participants were suffering from treatment-resistant chronic pain associated with one of the following:

- Traumatic injuries
- Congenital conditions
- Connective tissue conditions
- Chronic back pain
- Fibromyalgia syndrome
- Autoimmune disorders

Across a range of psychedelic substances and doses, pain scores improved substantially during and after psychedelic experiences, with participants reporting lasting pain reduction, improvements in their relationship with pain, improved pain management, improved physical functioning, and increased acceptance of pain.

In their interviews, participants reported being pleasantly surprised and even shocked at the perceived efficacy of their chosen psychedelic which, significantly, they used in conjunction with physical, psychological, and spiritual mindfulness-based practices including breathwork, journaling, meditation, yoga, and other mind-body-spirit movement practices. 

Out of thematic analysis emerged two processes in particular that may be integral to the positive outcomes of psychedelic self-medication for chronic pain: Positive reframing and somatic presence (“mindfulness of the body”). Positive reframing describes the user’s psychological state from despair toward acceptance and empowerment. Somatic presence, which refers to mindfulness of the physical effects of the psychedelic substance, was associated with lasting analgesia, reduced pain, and increased function.

Psychedelic-Induced Changes in Pain Perception 


Also in 2021, researchers at Maastricht University investigated the analgesic effects of LSD in a randomized, double-blind, placebo-controlled, within-subject study in which they administered 5, 10, and 20 micrograms of LSD on separate occasions to 24 healthy participants 1.5 and 5 hours after they had received Cold Pressor Test.

The aim of the task in this study was to submerge one’s hand in a cold water tank for as long as possible. Participants were encouraged to hold on as long as possible, however, they were allowed to remove their hand from the water as soon as they had enough.

A single 20 microgram dose of LSD significantly increased participants' pain tolerance by approximately 20% and decreased subjective ratings of painfulness and unpleasantness. Improvements in pain tolerance and subjective pain perception induced by LSD in this study were comparable to those induced by the opioid medications oxycodone and morphine, despite the relatively small dose. In conclusion, the researchers hypothesized that LSD’s activation of serotonin 2A and 1A receptors involved in pain perception may be central to the drug’s analgesic action. Stimulation of these receptors on serotonergic pathways from the raphe nucleus (a structure known to be involved in actions of descending pain inhibitory processes) to the spinal cord may change the way pain is perceived in the body.

The authors speculate that the analgesic effects of LSD could also be due pharmacological changes in the processing of nociceptive information, psychological changes in coping with pain, or the promotion of self-transcendence. 

Psychedelics for Pain: Summary


Preliminary evidence suggests that psychedelic substances, such as LSD and psilocybin-containing magic mushrooms, may be effective treatments for a variety of chronic pain conditions, including cancer pain, migraine, cluster headache, and phantom limb pain.

The severity of chronic pain and the relative ineffectiveness of conventional pain medications experienced by many patients has forced a significant number of sufferers to experiment with controlled substances for some relief. Despite their illegality, self-medication using psychedelics has become increasingly popular, and, as a result, a growing number of research institutions are investigating the analgesic action of these compounds.

It has been hypothesized that serotonergic psychedelics may affect pain perception by altering the activity of pathways that are central to the processing and modulation of pain. Further investigation is required to establish a more comprehensive understanding of how psychedelics exert their analgesic properties and improve the lives of chronic pain patients. Psychedelics have demonstrated clinical efficacy for several mental health conditions. If this therapeutic efficacy can be translated into the treatment of chronic pain, patients could experience potentially life-changing relief without having to engage in illegal activity or undergo invasive surgery.

That said, a lack of clinical research means that available evidence should be interpreted as preliminary until more methodologically valid and reliable studies investigating the efficacy of psychedelics for chronic pain are conducted. It is much too early to assume that psychedelics are efficacious treatments for the various forms of chronic pain. However, preliminary evidence looks promising and offers a beacon of hope for the chronic pain-stricken 20% among us. 

5-MeO-DMT

5-MeO-DMT (5-methoxy-N, N-dimethyltryptamine) is a short acting, serotonergic psychedelic, found naturally in the venom of the Sonoran Desert Toad (Bufo Alvarius). 5-MeO-DMT is gaining popularity as an effective tool for spiritual exploration and healing due to its extremely powerful psychoactive effects.

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5-MeO-DMT

Ayahuasca

What is unique about ayahuasca is that it is a concoction of two plants, the combination of which is essential for the ayahuasca experience. Combining two plants to use as medicine may not seem groundbreaking in and of itself, but the fact that if one is taken without the other, the experience is entirely different, and arguably non-existent, is what makes the discovery of ayahuasca so surprising.

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Ayahuasca

DMT

For millennia indigenous-American tribes have consumed N,N-dimethyltryptamine (DMT) as a key ingredient in sacred botanical brews, such as ayahuasca, and snuffs, such as yopo, as part of religious ceremonies in Central and South America.

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DMT

Ibogaine

Ibogaine is a naturally occurring indole alkaloid derived from the roots of an threatened species of perennial rainforest shrub called Tabernanthe iboga. Ibogaine, which is believed to have potent anti-addictive properties, has been used by the indigenous peoples of central west Africa for centuries.

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Ibogaine

Ketamine

Though ketamine gained a reputation for being dangerous and easily misused and abused, it wasn’t until 1999 that the US classified it as a Schedule III controlled substance. While it is often associated with the party scene, ketamine therapy is helping change the lives of many with severe depression, PTSD, OCD and even chronic migraines.

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Ketamine

LSD

In 1938, a Swiss chemist by the name of Albert Hofmann, working out of Sandoz Pharmaceuticals, became the first man to synthesize Lysergic Acid Diethylamide (LSD). Active at the microgram level (one-thousandth of a gram), LSD is the most potent psychoactive drug known to humankind.

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LSD

MDMA

The MDMA molecule bears structural resemblance to stimulants and some psychedelics, invoking feelings of euphoria, empathy, and boundless energy. MDMA also intensifies sensory perception, enhancing one’s appreciation of music and color which makes it one of the most popular drugs among festival-goers and electronic dance music fans alike.

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MDMA

Mescaline

In the 16th century, Spanish chroniclers attempted to eradicate ritual use of peyote cactus among indigenous American cultures, which led to the plant’s eventual prohibition in 1720. In the face of adversity, several indigenous communities righteously persevered, continuing and preserving their sacred practice in clandestine secrecy, and even managing to spread it widely over the last 150 years.

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Mescaline

Peyote

Peyote is a green spineless cactus that contains the classic psychedelic compound mescaline. Numerous Mesoamerican cultures, including the Huichol (Wixárika), the Cora (náayeri), the Tepehuanes, the Tonkawa, the Mescalero, and the Tarahumara (Rarámuri) have long regarded the plant as sacred, using it in spiritual and healing ceremonies for millennia.

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Peyote

Psilocybin

While shrooms were initially used for ceremonial purposes and spiritual awakenings, they have gained popularity for recreational use and current research on shrooms effects in a therapeutic setting is promising.

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Psilocybin

San Pedro

Since prehistory, San Pedro has been instrumental to Peruvian cultural traditions. in northern Peru in particular, it has been a tool to facilitate the shaman’s ‘‘journey’’ for healing purposes. Throughout this period, the visionary cactus has been known by many names, including huachuma or achuma.

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San Pedro
Decoration