A New Use for an Old Compound: Microdosing LSD to Reduce Fibromyalgia Symptoms

Summary

Microdoses of LSD may improve symptoms in a mouse model of fibromyalgia, a chronic pain condition. Female mice showed sustained reductions in pain-related facial expressions and sensitivity with intraperitoneal dosing, while oral dosing had quicker but shorter effects. Male mice benefited from both dosing routes. The study indicates that microdosing LSD could address pain perception and mood issues associated with fibromyalgia, though further research is needed to evaluate its potential in treating chronic pain.

Study at a glance

Abstract

Fibromyalgia (FM) is a chronic pain condition characterized by widespread pain, fatigue, sleep disturbances, and mood changes. Available treatments often provide limited relief, highlighting the need for new therapeutic approaches. Repurposing offers a faster and more cost-effective path to innovation. Lysergic acid diethylamide (LSD), historically known for its psychedelic effects, has recently re-emerged in clinical research. At very low "microdoses" LSD does not produce hallucinations but may still influence brain pathways involved in pain and mood regulation. We evaluated repeated microdoses of LSD in a well-established mouse model that reproduces key features of FM. Male and female mice with fibromyalgia-like symptoms received low-dose LSD either orally or by intraperitoneal injection for 12 days. We monitored overall health, pain-related behaviors, facial expressions of discomfort, sensitivity to touch and heat, and movement and anxiety-related behaviors. Safety was assessed through daily clinical observations and post-mortem organ examination. FM-model animals showed increased pain sensitivity, visible signs of discomfort, tremors, and reduced wellbeing compared to healthy controls. Microdosed LSD improved several of these measures in a sex- and route-dependent manner. In females, intraperitoneal administration produced sustained reductions in pain-related facial expressions and mechanical sensitivity. Oral dosing showed earlier but shorter-lasting effects. In males, both administration routes improved mechanical sensitivity and selected behavioral parameters. No major safety concerns were observed. These findings support the potential repositioning of microdoses of LSD as a treatment for FM. By targeting both pain perception and mood-related components, this approach may address multiple aspects of the condition. Further mechanistic studies and clinical evaluation are warranted to explore translational potential in chronic pain management.

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