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

In a mouse model of fibromyalgia, repeated very low doses of LSD (lysergic acid diethylamide) that do not cause hallucinations reduced pain-related behaviors and discomfort in a sex- and route-dependent manner. Female mice receiving intraperitoneal injections showed sustained reductions in pain-related facial expressions and mechanical sensitivity. Oral dosing produced earlier but shorter-lasting effects. Male mice showed improved mechanical sensitivity and selected behavioral parameters with both administration routes. No major safety concerns were observed. The findings suggest that microdosed LSD could potentially be repositioned as a treatment for fibromyalgia by targeting both pain perception and mood-related components.

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.