Relief from intractable phantom pain by combining psilocybin and mirror visual-feedback (MVF)

This case study (n=1) investigates the combination of psilocybin (0.2 – 3 g dried mushrooms) and mirror visual-feedback (MVF) to provide relief from intractable phantom pain. The study found that the Psilocybin-MVF pairing demonstrated synergistic effects in eliminating acute and long-term phantom-limb pain (PLP) and decreased the recurrence of its episodes.

Abstract

“AL’s leg was amputated resulting in phantom-limb pain (PLP). (1) When a volunteer placed her foot on or near the phantom – touching it evoked organized sensations in corresponding locations on AL’s phantom. (2) Mirror-visual-feedback (MVF) relieved PLP, as did, “phantom massage”. (3) Psilocybin-MVF pairing produced synergistic effects, complete elimination of PLP, and reduction in paroxysmal episodes. (4) Touching the volunteer’s leg where AL previously had external fixators, evoked sensation of nails boring through the leg. Using a “telescoping” nail, we created the illusion of a nail being removed with corresponding pain relief. (5) Artificial flames produced warmth in the phantom.”

Authors: Vilayanur Ramachandran, Chaipat Chunharas, Zeve Marcus, Timothy Furnish & Albert Lin

Summary

AL’s leg was amputated resulting in phantom-limb pain. Mirror-visual-feedback (MVF) and “phantom massage” relieved PLP, and psilocybin-MVF pairing produced synergistic effects, complete elimination of PLP, and reduction in paroxysmal episodes.

1. Introduction

About 95% of amputees experience phantom limb sensations, which are most commonly seen after limb amputation but can also occur for other body parts. The current era of experimental work on human patients was inspired, in part, by animal experiments.

In some patients, the arm is paralyzed after a few months, and the paralysis is carried over into the phantom. This phenomenon is dubbed “learned paralysis”.

The phantom limb is often fixed in a very painful position. By superimposing the reflection of the normal hand on the felt position of the phantom, the patient can create the illusion that the phantom arm has been resurrected, and thus alleviate the pain.

A class of neurons called mirror-neurons were discovered in 1996. These neurons fire when a person watches another person grab something, creating a virtual reality of impending action. Sensory mirror neurons in S2 and Anterior cingulate allow one to infer or empathize with the pain or tactile sensations, which are actually being delivered to another individual. However, we do not literally feel their pain.

We report some novel observations in a single patient AL, who was involved in a vehicular accident and had his right leg sacrificed. He was seen with phantom limb pain two weeks later.

2. Reorganization of the penfield map

AL had a map of his missing phantom toes, 15.24 cm proximal to the residual limb. Touching specific points on the map evoked sharply localized sensations in the phantom.

3. Mirror-action and phantom touch

We used a volunteer’s bare right leg to position the phantom, and AL felt localized touch sensations on the phantom when touch stimuli were delivered to the phantom.

AL experienced phantom pains several times a day, but was unable to move his foot out of a tightly hyper-dorsiflexed position. When he looked at V’s foot plantar-flexing, this caused an immediate, equivalent, flexing of the phantom, relieving his pain.

4. Psilocybin

AL attempted to treat the pain with opioids and Pregabalin, but the combined treatment produced marginal relief. AL tried including medicinal cannabis to his regimen, but the low initial effects prompted him to seek alternative treatments.

AL volunteered that he had been experimenting with mushrooms and noted a marked pain reduction. He tried mirror box therapy and psilocybin, and found that the combination of the two produced a striking 50% pain reduction and a complete elimination of paroxysms over a 2-week period.

AL tried different doses of psilocybin and felt that the mirror effect was synergistic with the psilocybin. The results need to be confirmed using placebo controls, but the onset of relief directly followed the MVF-psilocybin treatment makes the possibility of spontaneous relief unlikely.

Psilocybin, acting via serotonin 5-HT2A receptor, induces vivid cross-modal sensory experience and promotes neural plasticity including learning and cross-modal cortical-reorganization. Psilocybin enhances communication between visual and somatosensory systems, resulting in stronger both immediate and long-term effects.

5. Phantom fire

AL experienced phantom heat from an artificial flame, which relieved his phantom pain and made him feel as though he was “sitting next to a fireplace”. The delay in experiencing the heat is strongly suggestive of confabulatory response.

Insular cortex neurons with mirror-neurons-like properties may be activated by the sight of a flame touching someone else’s arm. This allows the subject to experience the warmth of the flame, which soothes the phantom and alleviates the pain.

“O, who can hold a fire in his hand, By thinking on the frosty Caucasus?”

A patient with a left arm removed will imagine warmth more readily than in his real hand. This challenges a hierarchical bottom up approach to brain function.

6. Mirror visual feedback

We tried MVF on AL, and found that viewing the reflection of his intact leg in the mirror, symmetrical movements, and massage of the intact leg, alleviated pain in the phantom leg on about half the trials.

7. MVF effects on dysuria

Al reported extreme pain during defecation, micturition, and ejaculation. After putting a mirror parasagittally to the right of the penis, the pain disappeared permanently.

8. Phantom pin removal

The authors examined a patient who had experienced frostbite as a child and experienced phantom-frostbite-like sensations as an adult. The patient experienced a metallic sensation sliding through his phantom foot when touching the precise point of the foot where nails had been placed.

9. Conclusions

We have demonstrated several new principles of brain organization by testing a lower-limb amputee with phantom limb pain. These principles include the plasticity of connections and inter-modular interactions, as well as the phenomenon of inter-subject synesthesia, which occurs for both touch and heat.

AL reported intense phantom pain during micturition, which was resolved by placing a volunteer’s foot in place of the phantom and “removing” the pins with a telescoping antenna.

Psilocybin reduced AL’s phantom pain after just 3 doses, and the reduction persisted for weeks and months following the procedure. This suggests that Psilocybin makes the brain more receptive to mirror therapy and makes the pain reduction last longer or even disappear.

The “standard model” of brain function requires a radical revision, as the brain is not a collection of independent, autonomous modules, but rather a symbiotic colony of brains that interact with each other, with the body, and with others.