Exploratory evaluation of encapsulated kratom using multimodal quantitative sensory testing in dogs

Kratom has experienced rapidly rising popularity in Western countries, particularly the United States where an estimated 10-20 million individuals use it for management of mental health conditions, performance enhancement, substance use substitution, and chronic pain conditions. Despite widespread anecdotal claims of analgesic benefits, robust preclinical data on kratom's efficacy remain limited, necessitating translational models to evaluate its potential. The objective of this study was to evaluate the analgesic efficacy of an encapsulated kratom extract compared to buprenorphine and placebo in healthy beagle dogs using quantitative sensory testing.

Eight healthy female spayed beagle dogs were included in this blinded, randomized, three-phase, crossover design following IACUC approval. Each dog received the following three interventions across the study period: encapsulated kratom extract by mouth at a 1 mg/kg target oral mitragynine dose, an oral placebo, or buprenorphine 0.02 mg/kg intramuscular. Each dog underwent baseline quantitative sensory testing and then at 0.5, 2, 4, 6, and 8 h post-dosing. Three doses of kratom and placebo were administered prior to sensory testing. Sedation scores were also obtained at each time point. Quantitative sensory testing outcomes were analyzed separately by modality using trimmed replicate means, with changes from baseline calculated for each dog and time point. Modality-specific minimum detectable change thresholds, derived from baseline within-time point variability, were used to classify meaningful responses. Treatment effects were evaluated using linear mixed-effects models (treatment, time, and sedation score as fixed effects; dog as a random effect), supplemented by summaries of peak change, time to peak, responder proportions, and trapezoidal area under the curve for both threshold changes and meaningful response burden.

Across QST modalities, buprenorphine elicited the largest threshold increases, with group-average peaks exceeding modality-specific MDC ₉₅ thresholds and high individual-dog responder rates (≥87.5%) in electrical, mechanical, and thermal tests; kratom produced modality-dependent effects, strongest in electrical QST (87.5% responders) and modest in thermal and mechanical.

These findings underscore the complex pharmacological profile of kratom, suggesting differential modulation of nociceptive pathways that warrants further investigation into its multiple alkaloids, active metabolites, and their specific contributions to the observed analgesic effect.