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Could Psychedelics Help Treat Chronic Pain?
Chronic pain affects millions worldwide and can be profoundly disabling. Despite how widespread chronic pain can be, current treatments are not effective for 40% of people, leaving a huge unmet need for alternative options.
While there are multiple approaches to pain management, such as physiotherapy, anti-depressants and psychotherapy, long-term use of commonly prescribed opioid-based analgesics has a risk for addiction.
While psychedelics have primarily been researched for their potential in the treatment of mental health conditions such as depression and anxiety, new research is now investigating psychedelics for the treatment and management of chronic pain.
Neuroscientist Dr. Grace Blest-Hopley, founder at Hystelica and Research Director at Heroic Hearts, has conducted recent studies on veterans and fibromyalgia patients that have shown improvements in chronic pain through psychedelic therapy.
The research focuses on an individual’s relationship to and interpretation of pain, Blest-Hopley tells States of Mind.
Neuroplasticity And Perception Of Pain
In the Heroic Hearts veteran study, initial results found that over 50% of 81 veterans that attended a retreat with either psilocybin or ayahuasca who had chronic pain no longer had symptoms after the retreat.
Additionally, the researchers note that those who did have continuing symptoms saw reduced severity and improved quality of life.
However, they also emphasise that how psychedelic retreats impact chronic pain in veterans has not yet been investigated – and importantly, how long these effects last for.
Blest-Hopley says that when we think about pain it’s important to think about its multiple components.
“Some of the pain comes from the tissue itself and the nerves within our body, but there is also the other side of it, which is our brain has to interpret the signals,” says Blest-Hopley.
“This is sometimes where we people get stuck in chronic pain, because the nervous system is heightened in its sensitivity. It is also part of our Default Mode Network — internal blueprint, the story that we hold about ourselves and tell ourselves.”
Blest-Hopley explains that, importantly, the veteran study study showed significant improvements in pain interpretation and relationship to pain, not any changes in actual tissue healing.
In this regard, psychedelics, particularly psilocybin, may hold promise in changing some of the maladaptive thought patterns associated with chronic pain and may improve pain perception.
An element of this is neuroplasticity — researchers note that maladaptive neuroplasticity plays a “crucial role in the maintenance of chronic pain, leading to neurons gradually becoming overly sensitive to pain stimuli.”
Pain and Inflammation
Psychelics may offer relief through our relationship and perception of pain, other theories suggest the compound may hold anti-inflammatory properties — that may play a part in modulating inflammatory pathways linked to chronic pain.
A study in mice found that a single dose of psilocybin relieved inflammatory pain and reversed mechanical sensitivity to pre-injury levels.
Blest-Hopley explains there’s potential that psilocybin is actually altering structure and function of the nervous system.
“What we’re really talking about is changing maladaptive thought patterns, changing how we perceive the pain,” says Blest-Hopley.
“So, we’re talking about potentially influencing some biological factors in terms of increasing neuroplasticity and neurogenesis that may also help with inflammation and neuro-inflammation.
“However, there’s also the psychological factors around like mood and stress and how we’ve been conditioned, as well as social factors such as the environment that we’re in and how much pressure we’re under.
“We think that there are a lot of interesting mechanisms.”
Breaking The Pain-Depression Cycle
Chronic pain is also closely linked to difficulties with mental health, causing people living with pain to experience depression, anxiety and reduced quality of life.
Recent data from the Heroic Hearts study suggests that US veterans who experience chronic pain experienced reduced symptoms after attending a psychedelic retreat.
Additionally, in 2025, researchers identified specific brain circuits impacted by psilocybin, offering new insight into ways to disrupt the pain-depression cycle.
Using mice with chronic nerve injury and inflammatory pain, the researchers discovered that a single dose of psilocybin reduced pain and pain-related anxiety.
Joseph Cichon of Penn University, senior author of the study, suggests that psilocybin may offer relief by bypassing the site of injury instead directly modulating brain circuits that process pain, alleviating both pain and the dysphoric mood caused by pain.
However, the research team highlighted that, while the findings are encouraging, it is unknown how long the effects last and what dosing is needed, urging for further research to understand safety and effectiveness.
“This new study offers hope,” says Cichon.
“These findings open the door to developing new, non-opioid, non-addictive therapies as psilocybin and related psychedelics are not considered addictive.”
Psychedelics for Chronic Pain Treatment?
In the 1960s and 70s, researchers investigated psychedelics for the treatment of cancer-related and phantom limb pain.
These early studies found that patients with cancer-related pain who were administered LSD experienced longer lasting relief compared to opioid-based pain killers. Even more, people with phantom limb pain experienced complete or partial resolution of their symptoms.
Psychedelic research was sanctioned by the US government shortly after, however, a resurgence of studies are now beginning to take another look at their potential uses in this area.
A recent review evaluated the current evidence on psychedelics for the management of cancer pain.
It found that while reduction in pain has not been widely measured as a primary outcome, classic psychedelics, including LSD and psilocybin, have demonstrated promise in potential management of cancer-related pain.
The researchers highlight the more than 20 trials investigating psychedelics for pain management including 14 investigating psilocybin, and two investigating MDMA, with the majority looking to understand their potential in cancer pain (not all of these studies are randomized controlled trials, so the researchers suggest more robust evidence in this area could be produced in the future).
While research is in its early stages, a number of further studies, including microdosing for chronic pain are now being carried out.
A recent analysis found that while results show potential for psilocybin as a treatment for chronic pain relief, many of the studies contain methodological issues and a “lack of high-quality evidence”.
So, in summary: the potential is promising. Relief could be coming for those in need. While remembering that current research is still limited and needs to be expanded in human clinical trials.
“Despite these limitations, the potential for psilocybin in chronic pain management is encouraging,” write the study’s authors.
Expert Board Member
Chronic pain is one of the most complex challenges in both neuroscience and clinical practice as it lives not only physically, but in the brain's interpretation of threat, shaped by memory, mood, and the nervous system's adaptation. Here, emerging research is explored, describing how psychedelics like psilocybin and MDMA appear to work by shifting the brain's interpretation of pain signals — disrupting maladaptive patterns through neuroplasticity. For those who have been failed by conventional treatments, this potentially represents a different approach to treating chronic pain.
