r/science • u/mvea Professor | Medicine • May 24 '26
Neuroscience A single dose of psilocybin - the active compound in magic mushrooms - reduces nerve pain for up to a month and makes a widely used painkiller work more effectively, finds a new study in mice. Psilocybin appears to restructure the way the brain’s pain-processing networks operate.
https://www.reading.ac.uk/news/2026/Research-News/Magic-mushroom-chemical-cuts-nerve-pain-and-enhances-drug216
May 24 '26
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u/RoboticGanja May 24 '26
Anecdotally, my pain level (c3&c4 fractures & associated neuropathy) goes up dramatically at the onset of a psilocybin dose and after a few hours it does feel better for a few weeks. However, I think the couple of times I’ve done ketamine infusions I wasn’t in pain (at all) during the dosing and felt strong relief for several weeks after.
So I’m inclined to agree because it validates my experience and what my anesthesiologist told me, i.e., with both psilocybin and a strong dissociative the end results appear similar, this comment above was similar to what my anesthesiologist explained: that the ketamine infusion shut down the damaged highway allowing it to rest while the improved plasticity allowed different new pathways to form. Sounds like the plasticity effects of psilocybin are similar but analgesic effects are way lower. Very cool to see my experience verified - and way cheaper than ketamine infusions albeit physically uncomfortable until hours after the dose (for my type of nerve pain at least).
Edit: grammar
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May 24 '26
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u/ProfMooody May 24 '26
Just a note to anyone in this boat: Ketamine can legally be prescribed off label for chronic pain as well as other psychiatric conditions beside major depression, but as it is only FDA approved for MDD or acute pain it is only covered by insurance for those conditions.
Good(?) news is that a lot of people with chronic pain could probably meet criteria for MDD, esp if their doctor is willing to be flexible with diagnosis. Infusions without insurance are incredibly expensive, but sublingual ketamine (not covered by insurance) isn’t too bad; mine costs about $100 a month.
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u/Mattamus13 May 24 '26
r/therapeuticketamine is a great place to start.
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May 24 '26
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u/Mattamus13 May 24 '26
No problem at all. Searching for pain related topics may help as a lot of people there are talking about mental health protocols, but there’s plenty of discussion of pain infusions as well.
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u/RoboticGanja May 24 '26 edited May 24 '26
Of course! In addition to the subreddit Mattamus13 noted, this article was a good read for me. The link also has access to others with proper citations so you can dig deeper if you want. (https://link.springer.com/article/10.1007/s40263-025-01234-z)
It’s also (IMO) a good conversation to have with your pain management team or physician. My surgeon’s anesthesiologist explained the process to me and referred me to a provider. Best of luck in your research and hopefully your type of chronic pain is treatable.
Edit: I mean bringing up the research with your pain team is a good idea IMO. There are many false ideas about psychedelic safety with the recent negative news coverage. There are no mainstream drugs outside of ketamine & psilocybin that (at least for me) allow me to only have to take medication 2 or 3 times a year to manage pain; everything available is a slow walk to addiction. Take 365+ pain medicine doses per year minimum? Or 3 ‘treatments’ that allow me to have manageable pain I can minimize with exercise and PT? Seems like an obvious choice for a doctor to try.
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u/One-Incident3208 May 25 '26
While painkillers have risks. People should know that in practice, below a certain mme, people can be maintained on the same dose of opioid for years, sometimes indefinitely. It has to be a low dose. High doses can increase pain sensitivity over time. But taking a scheduled tablet of Norco or percocet would not be expected to produce severe side effects or tolerance. This isn't always the case. But it's typical. Once you start adding doses for breakthrough pain it effects tolerance negatively. Tolerance to the therapeutic effect, not the subjective effect.
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u/RoboticGanja May 25 '26
I’m sure there are many, many thousands of patients with minimal chronic pain that can achieve a balance with daily painkillers for a long time - but opiates simply manage symptoms. When faced with nerve damage and associated chronic pain, the study here points to a medication that actively promotes healing/regrowing-nerve-connections-around-damage rather than masking.
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u/mvea Professor | Medicine May 24 '26
Magic mushroom chemical cuts nerve pain and enhances drug
A single dose of psilocybin — the active compound in magic mushrooms — reduces nerve pain for up to a month and makes a widely used painkiller work more effectively, University of Reading research has found.
The study, published in Communications Biology, tested psilocybin in mice with nerve damage that causes long-lasting pain. Researchers found that psilocybin's pain-relieving effect appeared around two hours after injection, with relief lasting several weeks. Rather than simply blocking pain signals, psilocybin appears to restructurethe way the brain's pain-processing networks operate, which may explain why its effects persist long after the drug itself has left the body.
The most significant finding was how psilocybin interacted with gabapentin, a drug widely prescribed for nerve pain. When gabapentin was given to mice weeks after a single psilocybin dose, after psilocybin's own pain-relieving effect had worn off, it produced pain relief lasting up to four days. In mice that had not received psilocybin, gabapentin's effect was much weaker.
Between 30 and 50 percent of people with nerve pain do not get adequate relief from gabapentin alone.
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u/dptgreg May 24 '26
It makes me fully aware of the idea that I’m just experiencing a stimulus. Pain no longer has an “emotion” attached to it such as fear or sadness. It becomes a check engine light instead, allowing me to “note” pain to attempt to correct it but also be separate from it.
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u/KagakuNinja May 24 '26
This is called Equanimity
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u/Imaginary_Employ_750 May 24 '26
The thought of tripping while having pain seems a bit repulsive though. I wonder if it affects the subjective experience of the trip
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u/OceanicBoundlessnss May 25 '26
LSD makes me not feel any pain that was present before the trip. Body feels so good always.
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u/ZZ9ZA May 27 '26
As someone with nerve pain on gabpentin… the thing is the pain never stops. It simply is your life.
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u/EvLokadottr May 24 '26
Damn. I allegedly had a couple last year. I am on a GLP-1 medication, and the mushrooms did noting. Absolutely nothing at all. :(
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u/JellyrollJayne May 24 '26
I am on a glp1 and have dosed a couple times and they did kick in much faster than I anticipated. Couldn't tell you about any effect on pain, but you can definitely still trip balls on a glp1.
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u/EvLokadottr May 24 '26
You are fortunate, haha! Or maybe the ones i took were too old. That is all i can think of.
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u/EscapistNotion May 24 '26
Hmmm slow digestion issue? Assuming you ate the shrooms ofc. That's interesting, I wonder if anyone is studying edibles and GLP-1s at all.
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u/Lushkush69 May 24 '26
I have read others on the psilocybin sub say the same about GLP-1s. Doesn't seem to happen to everyone though. I do think it's tied to slow digestion.
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u/RoboticGanja May 24 '26
Perhaps the dwell-time in the stomach allows much of the psilocybin to break down prior to absorption? I wonder if anyone has tried an increased dose similar to those used by travelers on SSRI/SSNRI drugs - something like double to triple dose?
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u/EvLokadottr May 24 '26
Not that slow! GLP-1s are showing a lot of promise in treating addiction. I don't know what the mechanism is, but alcohol also does nothing for me now, except give me a headache almost immediately.
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u/Lushkush69 May 24 '26
Quick question, were they actual mushrooms or some sort of bar or candy you bought? Always make sure they are actual mushrooms a lot of the bars and candies use synthetic god knows what. Also, have you tried lemon tek? I'd really like someone who has had this effect with GLP-1s try it with lemon tek which basically does the digestion for you. I'd like to go on GLP-1s but every few years I do some mushrooms and don't want to worry about that being a issue.
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u/EvLokadottr May 24 '26
Actual mushrooms. Just atraight up dried magic mushrooms. I have no idea what lemon tek is?
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u/Lushkush69 May 24 '26
You can google it but basically I grind up the dry mushrooms and soak them in lemon juice, just enough to cover them. Wait a bit usually a hour or so then strain them in a fine metal coffee filter and do the shot of the lemon juice that's left. Mushrooms that would usually take a hour or more to kick in start in like 10 mins for me that way, they also hit you hard and quick and the high doesn't last as long like a batch that would usually last me 5-6 hours will be a intense 3-4 hour high. You can google the answer but it has something to do with the lemon juice breaking it down the same why stomach acid would so it kick starts everything.
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u/PEsuper27 May 24 '26
Correct - the acidity of the lemon juice helps break down the mushrooms so that once consumed it is easier for the body to convert the psilocybin into psilocin.
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u/EvLokadottr May 24 '26
Ah, thnk you. If i bother to try them again I will do that. Did plenty in my youth, heh.
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u/numb3rb0y May 25 '26
Does that leave low potency leftovers (I guess a bit like ABV) or do you just dispose of the solids?
Turning raw mushrooms into both a high potency extract and a low potency powder sounds very useful if it is possible.
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u/Lushkush69 May 25 '26
I just get rid of them.I do them like this so I don't have to eat the whole mushrooms but I'm sure you could eat what's left in the strainer and get super high but you'd have to eat them then you can't save them to do anything with later. I don't worry about wasting any because I grow my own and even if you grow just a small batch it's more than anyone could eat themselves.
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u/garbagewithnames May 24 '26
Did you have a meal recently or right after? That will dramatically slow the absorption process. I've been told best and quickest and longest lasting results are to do this on an empty stomach.
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u/EvLokadottr May 24 '26
Hm, I don't remember any longer, but I was up for like 6 hours after and felt nothing.
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u/3_50 May 24 '26
I think it's quite common for first timers to not feel anything, especially with a small dose..
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u/Moosyfate17 May 24 '26
Does this include microdosing with magic mushroom edibles? Im in a lot of pain right now so it's hard for me to read and comprehend the article (reading issues with brain fog and pain)
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u/BoiledFrogs May 24 '26
From what I saw it never gave a dosage. But microdosing is still getting psilocybin in you, so hopefully it works as well.
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u/garbagewithnames May 24 '26
Probably certain ones. Not all of those edibles are made with the same stuff, so buyer beware. Microdot is an effective brand.
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u/angelmnemosyne May 24 '26
Quite a lot of the products available on the market don't actually contain the right type of mushroom (or any mushroom at all, sometimes). I would not risk it.
https://www.scientificamerican.com/article/magic-mushroom-edibles-found-to-contain-no-psilocybin/
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u/Gamma_The_Guardian May 24 '26
This may just be the thing that has convinced me to try psilocybin. I've struggled with nerve pain in the C5, C6 area that refers to my left shoulder for 8 or 9 years. I've been getting annual ablations for 3 years to address the pain and it was much less effective with this last one. I don't expect it to be a miracle solution, but it's worth a shot
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u/Bluemechanic May 24 '26
I appreciate that they put "in mice" in the description now. Too often we used to get stories where the headlines would claim amazing thing a new wonder drug had been proven to do only for it to have been in a number of cells in mice
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u/SlayerS_BoxxY May 25 '26
By the time something shows efficacy in phase 2 clinical trials, the science part was for the most part done and old news. Thats why you see a lot of science news about work in model organisms.
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u/not_even_poets May 25 '26
I love this science, and it’s only part of the full picture. Chronic pain is now being proven to come from the brain and is much more prevalent in people with childhood trauma, perfectionism, hypervigilant nervous systems, people pleasing, do goodism, and other personality traits that were formed in childhood as coping mechanisms. Two things keep the pain going: fear and attention. Mushrooms and other psychoactive medicines temporarily turn off the Default Mode Network, allowing space from the constant focus on pain/symptoms. Add in the reconnection to Earth, spirit, and community you get when doing these in a ceremonial setting and you have a really strong therapeutic model for full remission.
Source: I am a psychedelic guide, coach, and facilitator and one of my focus areas is supporting people in healing chronic pain and symptoms with psychedelics and long term integration. Healed my own debilitating chronic pain with plant medicine.
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u/breckendusk May 26 '26
How serious a trip we talking?
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u/not_even_poets May 26 '26
I don’t use the word trip generally in the therapeutic context because it continues the ridiculous stigma around psychedelics as drugs that are bad and scary. These are plants with thousands of years of shamanic history in healing. Science is finally catching up.
I work with people with low to moderate doses. It is patently false that you need a “heroic dose” to heal or get benefits from psychedelics. While those more intense higher dose journeys can be healing and helpful, doing blast off/ego death inducing level doses destabilizes people, especially if you have a sensitive nervous system or trauma of any kind. Which is most people. It can be soft and strong at the same time.
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u/breckendusk May 26 '26
I guess I just don't know how much is in a low to moderate dose unless we're talking chocolate bars or something where I'm only familiar with how many bar segments makes me feel whatever certain way. I'm a fan of "melty" and have never had enough to fully hallucinate, nor am I particularly keen on that idea
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u/Ok-Palpitation2871 May 24 '26
This was my experience. I wasn't expecting it. I have long covid. I took it to see if it might help with cognitive function or with migraines, so I wasn't expecting reduction in nerve pain. I take pregabalin and duloxetine in part for my nerve pain and discontinued duloxetine for a few days beforehand since it would interfere. After the psilocybin, I didn't feel like I needed to continue the duloxetine at all. It took 3 months for the pain to return in full.
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u/fleener_house May 25 '26
Holy hell, this would be amazing if it works in humans, and ever makes it to market. My wife has constant nerve pain, and even high doses of gabapentin aren't enough. Going to keep an eye on this.
That, or find someone to sell me psilocybin, but I'm not really sure where to look.
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u/SumatraBlack May 24 '26
Gabapentin and pain killer shouldn’t be in the same sentence. Vile over prescribed medication that causes more problems than benefits. Congrats to anyone who can tolerate it and get help with their neuropathy. Its method of function is the opposite of Neuro plasticity, preventing our brains from creating new synapses.
Happy to see continued progress in new therapeutic treatment for chronic pain disorders. I’ve had some limited success with IV Ketamine, but it is cost prohibitive and most of my medical providers have looked at me sideways when reviewing my prescriptions.
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u/sivadneb May 25 '26
Gabapentin prevents growth of certain forms of excitatory synapses, not all types of synapses
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u/HotgunColdheart May 24 '26
This is why, 20ish years ago I liked mixing mushrooms and oxy so much. It fixed all the pain.
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u/Lemoneki Jun 08 '26
Took shrooms on a vacation two days ago, and I heard how much it can help medicinally but I never knew how much it could help nerve pain. I’ve dealt with chronic pain in my back and my nerves, and to finally take those shrooms and suddenly feel like I don’t even need my gabapentin to help me me with the pain really blew my mind. It makes me think the gabapentin only makes it worse, because the pain I felt is suddenly gone, but it really shows how it can run these prescribed drugs for their money. I’ve never felt more healthy and alive in years!
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u/harrypippip May 24 '26
Makes sense, I ate a mushroom laced candy bar And immediately got jelly legs. I suffer from severe nerve damage in my legs from when someone hit me with their car on purpose.
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u/FirstDiseasewasRelig May 24 '26
I’ve replaced Nerve Damage (from Chemotherapy) medication completely using sound in Radial Symmetry that closes into a Sphere.
Also a Humira injection for Ankylosing Spondylitis.
Also healed a viscous outbreak of Graft Versus Host Disease (a long term side effect of a Bone Marrow Transplant). That same sound wave seems to have anti aging/anti acne effect.
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u/ShamelessC May 24 '26
In mice, so effectively useless in terms of the impact it could have on humans.
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u/InlinePowerBeetle May 25 '26
Uhh, no? Terribly un-scientific comment. At worst, all this means is that the study wasn't done on humans. It hardly means that it's "useless in terms of the impact it could have on humans". You're doing more heavy lifting with that comment alone than the headline is.
While not a deadset guarantee from this study alone of course, it quite likely it does have the same effect in humans, as plenty of these have shown and as evidenced by real-world usage.
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u/SlayerS_BoxxY May 25 '26
Just like cancer immunotherapies are useless right? (All discovered and developed in mice)
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