Inhibition of muscle sympathetic action potential firing and recruitment patterns following cannabis inhalation in humans

Cannabis is among the most widely used recreational substances, but the physiological consequences of acute and chronic use remain poorly studied. We recently demonstrated that acute cannabis use reduces muscle sympathetic nerve activity (MSNA). However, MSNA bursts comprise action potentials (APs) of varying size, which exhibit distinct firing and recruitment patterns that represent the communication between the sympathetic nervous system and the circulation. Applying a continuous wavelet transform to the microneurographic MSNA signal, we investigated the hypothesis that sympathetic AP firing patterns would be attenuated following cannabis inhalation at rest and during an end-expiratory apnea in young habitual cannabis users (<i>n</i> = 14; 7 females; 23 ± 3 yr). Following cannabis inhalation, MSNA burst occurrence and amplitude were reduced (all <i>P</i> < 0.001). Cannabis inhalation lowered the firing probability of medium-sized APs (normalized AP cluster 4: 78 ± 34 to 49 ± 31%; <i>P</i> = 0.03) and induced a derecruitment of larger AP clusters (22 ± 11 to 18 ± 9 clusters<b>;</b> <i>P</i> < 0.01). During an end-expiratory apnea following cannabis inhalation, there was an increase in MSNA burst frequency (8 ± 8 to 28 ± 10 bursts/min; <i>P</i> < 0.01), amplitude (51 ± 8 to 94 ± 34 AU; <i>P</i> < 0.01), AP frequency (74 ± 146 to 327 ± 387 spikes/min; <i>P</i> = 0.01), and the number of APs per burst (6 ± 5 to 10 ± 9 APs/burst; <i>P</i> = 0.03). However, the ability to recruit larger AP clusters (15 ± 11 to 16 ± 11 clusters; <i>P</i> = 0.57) and alter AP latency (1.23 ± 0.12 to 1.26 ± 0.17 s; <i>P</i> = 0.50) was absent. These data indicate that cannabis inhalation acutely decreases sympathetic AP firing and disrupts recruitment patterns in humans.<b>NEW & NOTEWORTHY</b> We examined the impact of cannabis inhalation on the firing and recruitment patterns of postganglionic muscle sympathetic action potentials (APs) in humans. We found that cannabis inhalation induced a derecruitment of larger, high-threshold APs, reduced the discharge probability and baroreflex control of medium-sized APs at rest, and impaired sympathetic AP recruitment during an end-expiratory apnea. Collectively, these data indicate that cannabis impairs the fundamental, homeostatic communication between the sympathetic nervous system and cardiovascular system.