Pain Without a Body: Psychedelics and Phantom Limb Pain
What decades-old studies can teach us about psychedelics, phantom limb pain, and neuroplasticity
When someone loses a limb, something strange and haunting can occur: sensation in that body part doesn’t go away. In fact, people often report an intense sense of pain, despite the limb no longer being there. This phenomenon, known as phantom limb pain (PLP), affects over 70 percent of amputees.
PLP reveals something remarkable about the brain. Rather than “deleting” the part of the brain responsible for representing the body part that is now gone, it holds on. There’s something beautifully eerie about this — the brain insists that that part of you is still there. But when that insistence causes pain, we must examine the question of if the brain can be taught to forget.
While there are current treatment options for PLP, such as opioids, anticonvulsants, and mirror therapy, these treatments offer mixed and often temporary results. Moreover, existing pharmacological treatments tend to focus on suppressing symptoms rather than addressing the underlying neural mechanisms driving PLP. Mirror therapy attempts to address the maladaptive sensorimotor representations driving PLP, but it still has limitations in how long the relief lasts and how consistently it benefits patients.
But in the 1960s and 70s, researchers briefly explored a strange and promising possibility: what if the psychedelic substance LSD could help alleviate the pains of PLP?
A handful of smaller scale studies found that low doses of LSD seemed to alleviate PLP. These findings were promising, but the momentum behind these early findings was cut short by the sweeping legal restrictions of the War on Drugs in the 1970s, and the research faded into obscurity.
Today, with new studies showing how LSD and other psychedelics can rewire dysregulated brain circuits for mood disorders, it’s worth examining this idea of LSD treating PLP within this context. PLP involves aberrant firing patterns in the brain, and psychedelics are known to reshape the brain’s connectivity. It follows that psychedelics may offer a way to reset the brain’s map of the body to help it let go of the lost limb.
This article explores the history of PLP and LSD research, and the neural mechanisms behind why and how LSD may help treat PLP.
Historical studies
During the 1950s and 60s, psychedelic therapy was primarily being explored for alcohol use disorder and end-of-life anxiety, with LSD at the forefront of early psychiatric research. In the context of this broader wave of experimentation, a small case series in 1967 reported that 5 out of 6 patients with PLP experienced significant relief after receiving LSD. Another study from 1977 found that 5 out of 7 patients with PLP receiving sub-hallucinogenic doses of LSD reduced their pain.
These findings were far from definitive. The studies had small sample sizes, lacked control groups, and came from an era before rigorous clinical trial design became standard. But they offered an interesting possibility: that psychedelics could modulate not just mood or perception, but also physical pain.
Unfortunately, when the Controlled Substances Act classified LSD as a Schedule I drug in 1970 (a designation reserved for drugs deemed to have “no accepted medical use”), most research ground to a halt. The question of whether LSD could treat phantom limb pain was left unanswered.
Now, over 50 years later, we have the tools and freedom to continue pursuing this research.
Much of the modern psychedelic renaissance has focused on mental health: psilocybin for depression, MDMA for PTSD, and ketamine for treatment-resistant mood disorders. But alongside these breakthroughs, researchers are slowly returning to a long-overlooked question: can psychedelics also treat pain?
One particularly compelling case emerged in 2018, when a patient with PLP reported that he had been experimenting with both mirror therapy and psilocybin. He said that psilocybin produced instant and long-lasting significant pain relief lasting 3 hrs, while mirror therapy alone had a lesser effect on his pain. Interestingly, when he combined PLP with mirror therapy, he reported a complete elimination of pain for the next 2-5 weeks. While this case is anecdotal, it was enough to spark further interest.
Now, clinical trials are underway testing psilocybin as treatment for PLP. More broadly, there is an increased interest in psychedelics treating chronic pain. One clinical trial examines using psilocybin for chronic pain, and researchers are beginning to map how psychedelics alter pain-related brain circuits in healthy subjects using modern tools like fMRI. Complementing the human work, the lab I’m working at uses a rat model to investigate how LSD modulates activity in a key brain region involved in pain processing.
After decades in the dark, the intersection of psychedelics and pain is finally getting the attention it deserves.
Why psychedelics for PLP?
To understand why LSD might help treat PLP, we need to look at what’s happening in the brain.
PLP isn’t caused by damage to the body — it’s caused by persistent activity and reorganization within the brain.
After an amputation, regions in the primary somatosensory cortex (S1) that once represented the limb may become hyperactive or reorganize in maladaptive ways. This process, known as cortical reorganization, is one of the proposed neural mechanisms behind PLP. Another mechanism is central sensitization, where the nervous system becomes hypersensitive to signals, amplifying pain in the absence of any injury.
In simple terms, the brain holds onto a version of the body that no longer matches reality — and that mismatch causes pain.
Studies have shown that LSD, like other classical psychedelics, modulates connectivity between the thalamus (a key relay for sensory input) and the somatosensory cortex, and increases overall neuroplasticity — the brain’s ability to rewire itself. It disrupts rigid patterns of neural activity and encourages the formation of new connections.
This “loosening” of entrenched patterns is one reason LSD and psilocybin are being explored for mood disorders like depression, where rigid neural circuits keep people stuck in negative thought cycles.
With PLP, a similar principle may apply. If the brain is trapped in a maladaptive sensory pattern of generating pain from a limb that is no longer there, LSD may offer a way to interrupt that loop, allowing the brain to update its internal representation of the body and form new, more accurate connections.
In other words, in the case of PLP, LSD may help the brain reconfigure the very circuits that produce it.
Concluding thoughts
Today, we have tools that researchers in the 1960s and 70s could only dream of. We can image human brain activity in real time and trace changes in neural connectivity. As excitement around psychedelic therapy research continues to grow, these compounds are being explored for an increasingly wide range of conditions, including PLP and chronic pain more broadly.
PLP is a condition rooted in neuroplasticity gone awry. The limb is gone, but the pain stays, because the brain insists that it’s still there. The brain, in its effort to make sense of loss, creates real suffering from absence. Psychedelics like LSD offer a neuroplasticity-based approach to a neuroplasticity-rooted condition, indicating their promising potential and the value of further research.