Current arthritis treatments often have side effects attributable to active compounds as well as routes of administration. Cannabidiol (CBD) attenuates inflammation and pain without side effects, but CBD is hydrophobic and has poor oral bioavailability. Topical drug application avoids gastrointestinal administration, first-pass metabolism, providing more constant plasma levels.
Methods
This study examined the efficacy of transdermal CBD for a reduction in inflammation and pain, assessing any adverse effects in a rat complete Freund’s adjuvant-induced monoarthritis knee joint model. CBD gels (0.6, 3.1, 6.2 or 62.3 mg/day) were applied for 4 consecutive days after arthritis induction. Joint circumference and immune cell invasion in histological sections were measured to indicate the level of inflammation. Paw withdrawal latency (PWL) in response to noxious heat stimulation determined nociceptive sensitization, and exploratory behavior ascertained animal activity level.
Results
Measurement of plasma CBD concentration provided by transdermal absorption revealed linearity with 0.6–6.2 mg/day doses. Transdermal CBD gel significantly reduced joint swelling, limb posture scores as a rating of spontaneous pain, immune cell infiltration, and thickening of the synovial membrane in a dose-dependent manner. PWL recovered to near baseline level. Immunohistochemical analysis of spinal cord (CGRP, OX42) and dorsal root ganglia (TNFα) revealed dose-dependent reductions of pro-inflammatory biomarkers. Results showed 6.2 and 62 mg/day were effective doses. Exploratory behavior was not altered by CBD indicating a limited effect on higher brain function.
Conclusions
These data indicate that topical CBD application has therapeutic potential for relief of arthritis pain-related behaviors and inflammation without evident side effects.
