Background
People with long-term HIV-1 suppression (PWH) suffer from inflammaging, characterized by chronic inflammation and immunosenescence. As cannabis smokers display immune beneficial effects such as lower inflammation levels we decided to investigate the anti-inflammatory properties of one of its major component, the cannabidiol (CBD) under a full-spectrum oil, on PWH.
Methods
Within the double-blind, randomized, placebo-controlled trial registered as NCT05306249 on ClinicalTrials.gov, we present herein encouraging results from the first 40 ART-treated PWH with undetectable viremia, encompassing 50% women (median time on efficient ART 20 years, median age 59-year-old). Half took 1 mg/kg twice a day of a full-spectrum, pharmaceutical grade, CBD oil for 12 weeks and the other half took a placebo medium chain triglyceride (MCT) oil. On enrolment and after 12 weeks, we analyzed 34 cytokine and chemokine levels in patients’ plasma using multiplex ELISA. In 16 women and 16 men, transcriptome from CD4+ and CD14+ cells were also evaluated using BRB-seq, followed by RT-ddPCR (droplet digital PCR).
Results
After 12 weeks of full-spectrum CBD, 12 out of 34 plasmatic proteins were less expressed in the whole cohort. Distinguishing the results by sex, we found that, while 12 out of 34 proteins were still downregulated in men, only 3 out of 34 were underexpressed in women. Regarding transcriptomic analyses in CD4+ cells, PWH from CBD arm displayed lower levels of pro-inflammatory cytokines. When analyzing men and women separately, 7 cytokines expression were reduced for men but only CXCL8 for women. In CD14+ monocyte transcriptome, CXCL8, IL1β, CCL3 and IL1α genes were less expressed in men whereas CCL5 was overexpressed. For women the only clear difference could be seen for the overexpressed CCL5 and underexpressed IL10. With ddPCR assays, men exhibited a lowered TNFα, IL6, IL1β and CXCL8 mRNA rate after CBD intake while only TNFα decreased in women.
Conclusions
Pharmaceutical grade full-spectrum CBD oil is associated with anti-inflammatory properties regarding mRNA and proteins. This suggests that CBD could help PWH mitigate their chronic inflammation but its effectiveness varies greatly according to sex. From a global perspective, this clinical trial opens the door to investigate full spectrum CBD intake potential for other diseases associated with chronic inflammation.
Table or Figure
