Magic Mushrooms For Pain Relief
“Have you ever considered using magic mushrooms for pain relief?” isn’t a question you may have heard a few years ago, but after a decades-long hiatus, research investigating the therapeutic utility of classic psychedelics, namely psilocybin (the active ingredient in magic mushrooms), lysergic acid diethylamide (LSD), and dimethyltryptamine (DMT), is in the midst of a long-awaited and eagerly anticipated second wave.
Although the Controlled Substances Act of 1970 placed all psychedelics into schedule I, defined as having high addiction potential and no accepted medical use (which, for psychedelics, is not true), the consequential criminalization of scientific research and personal use failed to wane public interest.
If anything, the unscientific restriction and sensationalized degradation of these fascinating compounds perhaps served merely to add to the mystique surrounding their apparent boundary dissolving, mystical experience inducing power, and associated therapeutic potential.
The lesson that should have been learned here by president Richard Nixon’s racially motivated banning of these psychedelic “consciousness expanders”? And by all proponents of the drug war since its declaration? Purposeful suppression of that which you do not like does not make it go away — quite the contrary.
Fast-tracked by seminal work conducted by Dr. Roland Griffiths and his amazing team of skilled scientists at the Center for Psychedelic and Consciousness Research at Johns Hopkins, controlled psychedelic investigation is back, and it’s booming.
Encouraged and enthused by Hopkins’ unprecedented study in which almost 70% of participants found their magic mushroom experience to be one of the most spiritually significant and personally meaningful of their entire lives, research labs all over the globe are extending our knowledge of the true potential of psychedelics. In just the last few years, psychedelic-assisted psychotherapy has more than proven its efficacy as a treatment for a range of psychiatric disorders, from anxiety and depression to post-traumatic stress disorder and substance abuse disorders.
With Johns Hopkins, Imperial College London, New York University, and the Multidisciplinary Association for Psychedelic Studies, to name but a few of a plethora of institutions, all investigating psychedelics’ clinical efficacy in mental health conditions, a growing number of psychedelic companies, eager to contribute to this exciting field of study, are beginning to investigate psilocybin’s potential utility in pain medicine.
Magic Mushrooms for Pain Relief: The Evidence
Since Dr. Griffiths and his colleagues ignited the so-called psychedelic renaissance, researchers have very much focused on the ability of psychedelics, in conjunction with psychotherapy, to successfully treat psychiatric disorders. As a consequence, there has been very little scientific exploration into the pain-relieving properties of these intriguing compounds.
Much of the evidence suggestive of psychedelics’ analgesic effects comes from poorly controlled case reports that were published over half a century ago. Irrespective of the fact that past publications do not stand up to the rigorous designs of present-day scientific investigation, many findings were at the very least interesting, with some displaying tremendous promise, despite their unreliability and the absence of replication.
That said, there has been growing interest in psychedelics among pain medicine experts, and several recent preliminary studies appear to support the encouraging case reports from the 1960s golden era of psychedelic research.
Many of the earlier studies exploring the analgesic potential of psychedelics use LSD, however, as LSD and psilocybin are very similar both phenomenologically and pharmacologically, it is possible and most likely probable, that these compounds have analgesic properties in common.
Magic Mushrooms for Pain Relief: Cancer Patients
To use the famous words of the first person to both synthesize and ingest LSD (read Frshminds story “LSD and Managing Mental Health” for more background), Dr. Albert Hofman, a pain researcher by the name of Dr. Eric Kast experienced a “peculiar presentment” in the 1960s that LSD could be an effective pain treatment. Having observed LSD’s apparent interference in one’s capacity for selective attention, Kast hypothesized that preoccupation with the fantastical visions and sensations induced by the drug may help those who suffer to become less burdened by their pain.
Dr. Kast and his colleague, Dr. Vincent Collins, investigated this hypothesis by comparing the pain-relieving effects of LSD with hydromorphone (Dilaudid) and meperidine (Demerol), two well-established opioid analgesic medications, in a cohort of cancer patients.
Patients were administered a moderately strong dose of 100 micrograms at least 12 hours after they had received both of these powerful pain-killing opioids, and asked to report the perceived analgesic effectiveness of each drug. Results revealed that participants experienced significantly more pain relief under the influence of LSD compared to hydromorphone and meperidine, with many becoming completely pain-free for 3 weeks.
Rarely, if ever, is it seen in pain medicine that patients become completely pain-free. Even more extraordinary, is the fact that the lasting pain relief observed by Kast and Collins came about from a single, solitary dose of LSD.
Unfortunately, over the next ten years, only a couple of additional studies touched on the potential application of psychedelic substances in pain medicine. Incidentally, these studies were led by revered and prominent figures in the history of psychedelic research — Walter Pahnke and Stanislav Grof, and both produced impressive results.
In these preliminary studies, which took place 4 years apart, LSD-assisted psychotherapy, again delivered to terminal cancer patients, was shown to improve:
The curious case of phantom limb pain
After a tragic vehicular accident, internationally renowned UC San Diego scientist Albert Lin suffered a complex fracture below his right knee and was unfortunately forced to have his leg amputated. He was subsequently afflicted with severe phantom limb pains that tormented him on multiple occasions every day.
Having received no relief using standard pain medications, and marginal relief with anticonvulsants, Lin experimented with medicinal marijuana for a brief period, but again, he was left dispirited with excruciating pain. After experiencing some promising effects using mirror box therapy, a treatment employed all over the world for complex regional pain and phantom limb pain, also incidentally discovered by his colleague at UC San Diego, Dr. Ramachandran, Lin decided to try a single large dose of psilocybin-containing magic mushrooms.
Eventually, after many painstaking trials and what must have seemed at that stage like inevitable errors, Dr. Lin finally noticed profound relief lasting 3 hours after ingestion of these mushrooms. This fungal medicine, used sacramentally by indigenous communities for millennia, had lived up to its nickname. “Huh”, Lin was surely pondering, “these really are magic.”
The use of psilocybin alone also produced major reductions in pain at the onset of its psychoactive effects, but, unfortunately for Lin, relief dwindled and intense phantom pain returned once the psychoactive effects of psilocybin had subsided.
However, when psilocybin was combined with mirror box therapy, Dr. Lin experienced a monumental 50% pain reduction lasting 5 weeks, and complete elimination of paroxysms lasting 2 weeks. Pain reduction from this combination therapy was so profound that Dr. Lin was able to drop it altogether. Amazing.
Dr. Lin’s story, which can be found here in a paper published by the man himself in cooperation with Dr. Ramachandran and colleagues, provides support for a 1977 case series describing the experience of 7 phantom limb pain patients administered “sub-hallucinogenic” doses of LSD. During this trial, which was 2 months long in total, patients received 25 micrograms of LSD for 7 consecutive days before researchers increased the dose to 50 micrograms for 14 consecutive days after that.
In this case series, pain significantly improved in almost 80% of patients after LSD administration despite dramatic decreases in daily use of analgesic medication.
Magic Mushrooms for Pain Relief: Cluster Headaches
Cluster headache is often considered the most painful of all headache types, affecting approximately 0.1% of the population. Characterized by severe pain, cluster headache can be either episodic (occurring for periods of 1 week to 1 year), or chronic (occurring constantly for over a year).
Abortive treatments, that is, treatments that are used to quickly suppress attacks during cluster periods, including oxygen and sumatriptan, and Neuromodulators like verapamil, lithium, and corticosteroids, have thus far failed to demonstrate efficacy, providing mere marginal to no relief in most patients.
In 2006, assistant professor of psychiatry Dr. Andrew Sewell and his fellow researchers at Yale published the results of 53 interviews with patients who had used psilocybin or LSD to treat their cluster headache condition. Highlights of the author’s final analysis include:
- 22 of 26 psilocybin users reported that psilocybin aborted attacks
- 25 of 48 psilocybin users reported cluster period termination
- 7 of 8 LSD users reported cluster period termination
- 18 of 19 psilocybin users reported remission period extension
- 4 of 5 LSD users reported remission period extension
Additionally, 90% of psilocybin-using participants reported that psilocybin terminated their cluster attacks within just 20 minutes of ingestion, and 52% of participants who used psilocybin as a preventative measure reported that it did so effectively.
Of course, there are several limitations to this study that must be considered. For example, the collected data relies heavily on the retrospective reports of subjects, which may be subject to recall bias. The possibility of selection bias, the issue of recruiting subjects via the internet, and the absence of blinding also raise some potential issues, and so these findings must be regarded as preliminary. However, the impressiveness of participants’ reports should not be disregarded considering the notorious intractability of cluster headaches.
Clusterbusters, Inc., a non-profit organization dedicated to the education and research of cluster headaches, administered a similar survey almost 10 years later, the only difference being its incorporation of questions intended to further understand all types of cluster headache treatments. The final analysis of the Clusterbusters survey produced the following eye-catching findings:
- Psilocybin was completely effective as an abortive therapy in 30% of respondents
- Psilocybin was at least moderately effective as an abortive therapy in 70% of respondents
- Psilocybin prevented cluster attacks in approximately 40% of respondents
- Psilocybin deemed at least moderately effective as a prophylactic by 70% of respondents
Interestingly, a substantial proportion of respondents from the above surveys reported profound pain improvements from the use of sub-hallucinogenic doses of LSD or psilocybin, which is suggestive that the apparent pain-relieving properties of psychedelic compounds may be unrelated to their psychoactive effects.
To extend understanding as to whether or not this may be the case, a team of pain researchers from Hannover Medical School, led by head pain physician Dr. Matthew Karst administered the non-hallucinogenic lysergic acid derivative, ‘BOL-148’, to 4 cluster headache patients three times over 15 days.
In this study, BOL-148, which, incidentally, was also synthesized by Albert Hofmann, terminated cluster periods, extended remission periods, reduced cluster attack frequency, and displayed an ability to transition from chronic cluster headache to episodic.
Preliminary evidence of psilocybin’s migraine treating potential
Migraine is one of the top three diseases in the world, affecting approximately 12% of the US population and up to 15% of the global population. This is perhaps unsurprising considering the lack of effective treatments currently available for patients suffering from migraine, all of which are associated with unwanted side effects.
The lack of efficacious medication makes it incredibly difficult for patients to alleviate their pain. Naturally, this has prompted migraine sufferers to self-treat with psychedelic substances, who, having become fed up with the ineffectiveness of conventional treatments, are willing to break the law to find relief.
A qualitative analysis of data taken from three online psychedelic forums has provided unique insights into the potential utility of psilocybin as a migraine treatment. Contributors to the forums, all of whom had experienced no relief from conventional migraine medication, reported the following experiences using psilocybin to treat their migraine-induced pain:
- Reduced frequency of migraine attacks
- Reduced-intensity of migraine attacks
- Prevention of migraine attacks
Some users even experienced full remission.
Two years ago, the first placebo-controlled study exploring the migraine-suppressing effects of psilocybin took place. In this study, psilocybin significantly outperformed placebo (microcrystalline cellulose) in a cohort of adults aged 21-65 years.
Specifically, psilocybin produced much larger reductions in migraine days, reduced pain severity more effectively, reduced migraine-induced functional impairment, and increased weekly migraine abortive days.
Mechanisms of Action
Although psilocybin demonstrates efficacy as a pain treatment, certainly enough to warrant further scientific investigation, the mechanism of action responsible for its analgesic power remains a mystery;
Because biotech companies and investors are mostly interested in the development of drugs and novel treatments from which huge profits can be made, funding is provided for psychedelic studies that are largely geared towards clinical outcomes, and ensuring that psychedelics like psilocybin and related derivatives are safe and efficacious in patients.
Unfortunately, this leaves a lack of funding for mechanistic research that would help to extend our understanding of how psychedelics interfere with the signaling and processing of pain (ie discovering why using magic mushrooms for pain relief seems to work). This lack of interest and consequential lack of funding for mechanistic studies leaves us in the dark regarding the process behind psilocybin’s analgesic action.
The Psychedelic Experience
Researchers have however generated a few hypotheses that could explain why those using psilocybin or magic mushrooms for pain relief seem to show positive results.
Psilocybin initiates the psychedelic experience, often characterized by a sense of oneness with the universe, ego-dissolution, and revelatory psychological insights, via its activation of the 5-HT2A serotonin receptor. More specifically, it is thought, psychedelic activation of this receptor influences activity in an interconnected network of brain regions called the Default Mode Network (DMN) that are involved in the regulation of emotion, cognition, memory, and self-awareness.
Just as Dr. Eric Karst hypothesized in 1964, psilocybin may possess the power to switch one’s attention away from his or her pain, focusing it instead on the brightly-colored and inexplicably informative visions that are so often occasioned by these mysterious compounds. Some researchers believe that this re-allocation of attention from pain to the psychedelic effects could be one explanation for the success people report in using magic mushrooms for pain relief.
Interestingly, dysfunctional communication between these DMN brain regions is associated with the perception of several chronic pain states. Therefore, it is also possible that inhibition of activity in the DMN initiated by psilocybin may influence these very brain regions implicated in pain, causing an analgesic effect.
The role of serotonin receptors in pain modulation
Psilocybin does not exclusively activate the 5-HT2A receptor as it is active at a host of other serotonin receptors in the central nervous system involved in peripheral and centrally mediated pain processes. In particular, psilocybin activates both the 5-HT2A and 5-HT7 receptors in a group of neurons called the ventromedial nucleus of the spinal cord that plays an important role in informing the brain about potentially harmful stimuli.
Research has demonstrated that an injection of serotonin into the spinal cord region has antinociceptive effects, meaning that it can block the detection of painful stimuli, and, as a consequence, the sensation of pain. Selective serotonin reuptake inhibitors, a class of antidepressants that elevate serotonin levels, are often prescribed for a variety of different pain conditions. This suggests that psilocybin, which also elevates serotonin levels, could treat pain in this way.
Rat studies have shown that LSD may be an antagonist of 5-HT1A receptors located in the dorsal raphe, a brain nucleus important for the modulation of pain. The dorsal raphe’s descending pathways inhibit pain responses, and its ascending pathways modulate the responses of pain receptors called nociceptors in the thalamus.
Mechanistic studies in which 5-HT1A and 5-HT2A receptors are blocked before psilocybin administration are needed to investigate which of these receptors, if any, are involved in psychedelics’ influence on the processing of pain in these brain regions.
Is Psilocybin Anti-Inflammatory?
Recent research conducted by David Nichols, pharmacologist, medicinal chemist, and founding president of the Heffter research institute, suggests that psychedelic compounds, due to their activation of 5-HT2A receptors, may be effective treatments for inflammatory diseases.
It is thought that the anti-inflammatory properties of psilocybin lie in its ability to regulate tumor necrosis factor (TNF), a protein in the body that causes inflammation and is implicated in a variety of inflammatory conditions. Psilocybin could act similarly to anti-TNF antibodies, and consequently, may prove effective in the treatment of inflammatory conditions like rheumatoid arthritis, lupus, and Behcet’s disease
Plans in Place To Study Psilocybin’s Pain-Relieving Potential
UC San Diego’s Arthur C. Clarke Center for Human Imagination has collaborated with the Departments of Anesthesiology and Psychiatry to launch the Psychedelics and Health Research Initiative (PHRI). Together, they aim to study psilocybin’s ability to treat pain and promote healing.
According to rehabilitation and pain medicine physician, Dr. Joel Castellanos, an upcoming randomized placebo-controlled trial at UC San Diego is investigating whether the administration of two doses of psilocybin could be effective in patients suffering from phantom limb pain secondary to an amputation.
The UC San Diego researchers also plan to publish a case series in the coming year detailing the experiences of individuals using magic mushrooms for pain relief. Castellanos and colleagues have received a plethora of reports from individuals who have come to the same realization that he and his colleague Dr. Albert Lin did — Psilocybin can relieve pain.
An advantage to case series is that people suffering from chronic pain who provide the reports for the case series know their bodies more intimately than anyone else, including what treatment they respond to. So, obtaining information from a significantly large cohort of respondents as to how they manage to improve their pain can inform the design of future studies including the types of therapies that may augment psychedelic sessions.
Perhaps some kind of movement therapy or bodywork could play the same supportive role as humanistic talk therapy does in the treatment of mental health conditions.
Another chronic pain condition that physicians at UC San Diego are looking into is complex regional pain syndrome (CRPS), of which there are two types. Type 1 CRPS is typically caused by an otherwise innocuous injury, and, for reasons yet unknown, the nervous system gets into a positive feedback loop causing severe, disproportionate pain that is often accompanied by changes to skin color, decreased range of motion, and allodynia (pain when there shouldn’t be pain present). Type 2, on the other hand, is caused by a specific nerve injury.
A lot of different theories exist regarding the pathophysiology of CRPS, and a lot of different treatment approaches are employed as a result, including mirror box therapy and desensitization therapy, not to mention the variety of different medications. As of now, bisphosphonate medications that are used to treat osteoporosis have displayed the highest efficacy for CRPS.
However, as CRPS is predominantly driven through the sympathetic nervous system, researchers hope that serotonergic psychedelics such as psilocybin may facilitate a resetting of that process, in a way not too dissimilar from how they appear to “reset” the brain in patients with anxiety and depression. Should psilocybin prove to be effective in phantom limb pain, the research team at UC San Diego plan to continue studying the effects of psilocybin on a range of chronic neuropathic conditions including neuropathic pain from stroke and spinal cord injuries.
In a recent conversation with Dr. Lynn Marie Morski of the psychedelic medicine podcast, Josh Woolley, Associate Professor in Residence in the Department of Psychiatry and Behavioral Sciences at UCSF, revealed that he, in collaboration with Dr. Boris Heifets of Stanford and Dr. Michael Silver of UC Berkeley, is preparing a trial to investigate psilocybin’s effects in patients with chronic low back pain. Woolley hypothesizes that psilocybin could change how people relate to pain and may experience significantly less impairment as a result.
Also, a California-based startup called Tryp Therapeutics is exploring chronic pain relief using psilocybin and Tryp-8803, an off-the-shelf, 25 milligrams, proprietary psilocybin derivative. Tryp Therapeutics have teamed Dr. Robin Carhart-Harris, formerly of Imperial College London, and Dr. Dan Clauw of the University of Michigan, one of the world’s leading fibromyalgia experts, to discover effective treatments for a specific type of pain called nociplastic pain, which, by all accounts, is desperately required.
The treatment and management of chronic pain conditions pose a global healthcare problem. With conventional pharmacological therapies such as opioids failing to provide sufficient relief and proving to be problematic in many cases, there is an unmet need to discover novel treatments for debilitating and excruciating pain conditions.
Despite there being as yet insufficient evidence to support the clinical efficacy of psilocybin or magic mushrooms for pain relief, the preliminary evidence emanating from the few studies and case series that do exist in the literature supports further investigation, and perhaps more importantly, inspires hope for patients in pain.
If future studies demonstrate psilocybin’s ability to promote neural plasticity, reduce pain, and have positive effects on pain patients’ recovery, psilocybin-assisted therapy could be a game-changer for pain medicine, and we may just see a wider acceptance of using magic mushrooms for pain relief.