Psychedelics as Novel Therapeutics for Chronic Pain in Veterinary Medicine: A Hypothesis-Driven Protocol Using Low-Dose 1-Cyclopropionyl-D-lysergic Acid Diethylamide (1cp-LSD) in Canine Osteoarthritis

Low-dose psychedelics have shown potential in modulating chronic pain in humans, yet their application in veterinary medicine remains unexplored. This study protocol proposes to investigate the therapeutic potential of low-dose oral administration of 1-cyclopropionyl-D-lysergic acid diethylamide (1cp-LSD), a legal LSD analogue in certain countries, for the management of chronic pain in privately owned dogs with osteoarthritis. The study will employ a randomized, placebo-controlled design with caregivers blinded to treatment allocation. A cohort of about 24 dogs previously diagnosed with osteoarthritis, will orally receive sub-perceptual, intermittent doses of 1cp-LSD over a 30-day period, while maintaining their standard analgesic regimens to safeguard animal welfare. Outcome measures will include the Canine Brief Pain Inventory and caregiver-reported assessments, including the Treatment Expectation Questionnaire (TEX-Q), to evaluate both pharmacological efficacy and the influence of caregiver expectations as an indirect indicator of placebo effects as a secondary aim. The study anticipates a reduction in pain scores among treated dogs, potentially modulated by caregiver expectations. However, the sustained effect of 1cp-LSD in osteoarthritis remains uncertain due to interactions with inflammatory mediators. Limitations include the lack of established dose-response relationships, small cohort size, and variability in caregiver perceptions, which will be analyzed descriptively. The protocol establishes a comprehensive and methodologically framework to evaluate both the pharmacological therapeutic effects of low-dose psychedelics in managing chronic osteoarthritic pain and the psychological factors that may influence perceived outcomes.