Feasibility and Tolerability of Psilocybin for Phantom Limb Pain

This is a phase 1, randomized, placebo-controlled feasibility/pilot study,

• 9 people with phantom limb pain (PLP) were randomized to a single 25 mg oral dose of psilocybin (n=5) or 100 mg niacin placebo (n=4). Participants had one limb amputation and PLP.

• Primary finding: feasibility and tolerability. The authors found that administering 25 mg psilocybin with psychological preparation, monitored dosing and post-dose integration was feasible. This is the main finding of the study.

• No serious safety signals. There were no serious adverse events and no emergent suicidality. Transient increases in blood pressure and heart rate occurred after dosing but resolved spontaneously before discharge

• Expected acute effects occurred. Anxiety and psychological/physical discomfort were reported in both groups and resolved without intervention. In the psilocybin group, 2 participants reported nausea and 3 reported headache.

• There was a preliminary signal for reduced phantom limb pain. Self-reported weekly PLP intensity showed trends toward >30% reductions at both 2 and 4 weeks after psilocybin. However, the authors explicitly caution that these observations may be attributable to the very small sample and functional unblinding.

• Blinding is a major limitation. Because the subjective effects of psilocybin make treatment allocation relatively easy to identify, expectancy effects could have influenced self-reported pain outcomes. This substantially limits interpretation of the apparent analgesic signal.

The important distinction is that the study does not demonstrate that psilocybin is effective for phantom limb pain. Its conclusion is that the findings justify a larger trial investigating efficacy and potential mechanisms of serotonergic psychedelics in refractory pain syndromes

Abstract

Phantom limb pain (PLP) is a refractory condition defined by pain experienced in a missing limb. Psilocybin, a classical serotonergic psychedelic drug, can alleviate various treatment-resistant disorders but has scantly been investigated for chronic pain. This placebo-controlled, double-blind, randomized clinical pilot trial (NCT05224336) tested the feasibility, tolerability, and preliminary safety of psilocybin in individuals living with PLP. Nine participants (mean±SD 37±13 years) with one amputation and PLP were randomized to receive a single 25-mg oral dose of psilocybin (n=5; 2 female) or 100-mg niacin (n=4; 2 female). The dosing sessions were supervised by two monitors who met with participants during three pre-dosing preparatory sessions and a 1-day post-dosing integration session. Suicidality was assessed across all visits. Blood pressure (BP), heart rate (HR), and adverse drug effects were assessed during the dosing session. Headache was evaluated during the dosing and integration sessions. No emergent suicidality or serious adverse events were observed. In both groups, adverse drug effects (anxiety, psychological/physical discomfort) and transient elevations in BP and HR after drug administration resolved spontaneously prior to discharge. After psilocybin administration, two participants reported nausea and three reported headache. Exploratory self-reported ratings for weekly PLP intensity showed trends toward reduction (>30%) two- and four-weeks post-psilocybin administration but these effects may be attributed to the small sample size and functional unblinding. This is the first trial providing evidence of the tolerability of a 25-mg oral dose of psilocybin for PLP, a debilitating, enigmatic and treatment-resistant chronic pain condition.

Dean JG, Hurwitz E, Furnish T, et al. “Feasibility and Tolerability of Psilocybin for Phantom Limb Pain.” The Journal of Pain. 2026; online ahead of print, 7 August 2026. DOI: 10.1016/j.jpain.2026.106404. Read Paper

For more psychedelic news and research, visit the psychedelic health professional network homepage.