THC exposure alters ventilation after cervical spinal cord injury

Cervical spinal cord injury (SCI) disrupts descending respiratory drive and reduces ventilatory capacity (Berlowitz et al., 2016). Approximately 25% of those living with SCI report the use of cannabis to improve sensorimotor function, mood, and pain (Acland, 2018). Cannabinoids, which primarily signal via CB1 and CB2 receptors in the central nervous system, can modulate spinal motor output (Haynes et al., 2023) in locomotor circuits where CB1 activation enhances rhythmic activity and supports long-term plasticity (Kyriakatos and El Manira, 2007). Reports of cannabinoid influence on respiratory control networks are conflicted and whether similar processes influence respiratory motor recovery after SCI is not known. Here, we tested whether inhaled Δ 9 -tetrahydrocannabinol (THC) improves the trajectory of ventilatory recovery after cervical SCI. Adult male Sprague Dawley (n = 4 / group) rats received a C2 hemisection and were assigned to three exposures over the course of a week of THC vapor (50mg/mL in propylene glycol) or vehicle (propylene glycol alone), each delivered as 10 puffs (5 s puff every 3 min). Rats underwent whole-body plethysmography in room air (21% O 2 , 79% N 2 ) and during hypercapnic–hypoxic chemostimulation (10% O 2 , 7% CO 2 , 83% N 2 ). Ventilatory variables included: tidal volume (VT), minute ventilation (VE), breathing frequency (fR), inspiratory (Ti), expiratory (Te), total breath (TTOT) time, mean expiratory and inspiratory flow (MEF, MIF), and [Formula: see text]CO 2 . Baseline measurements occurred at −3 days (pre-injury), with follow-up on post-injury days 7, 9, and 11, including both pre- and immediately post-exposure measurements each day. Data were analyzed using a linear mixed-effects model. Recovery of ventilation across days was evident in both groups, consistent with previously described plasticity after cervical spinal injury (Fuller et al., 2008). However, THC exposure altered the temporal profile of recovery for several ventilatory measures. Significant Group × Day interactions emerged during chemostimulation for breathing frequency (fR), inspiratory timing (Ti), total cycle duration (TTOT), and flow indices (p < 0.05). On days with significant interactions, most consistently days 9 and 11, THC-treated rats exhibited lower fR and a shift toward longer Ti and TTOT, along with attenuated flow responses, relative to vehicle controls. In room air, these interaction effects primarily reflected post-exposure increases in Ti and TTOT compared with vehicle. Together, these findings suggest that THC alters specific timing- and flow-related components of the respiratory response, rather than producing uniform changes in ventilation. Our preliminary findings indicate that inhaled THC is associated with altered ventilatory recovery after cervical SCI. This divergence in timing- and flow-related measures suggests that cannabinoids may negatively influence pathways involved in respiratory motor adaptation. Additional experiments and histological analyses will help determine whether THC-related differences correspond to changes in spinal or supraspinal circuits involved in respiratory compensation. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.