Cannabinoids have been used for centuries for recreation and medicinal purposes
Medical cannabis refers to the use of marijuana-derived products prescribed by clinicians to manage various conditions. Emerging data, along with common believes by the public that the marijuana-derived non-psychoactive compound CBD is beneficial, place CBD as a promising therapeutic compound for alleviating disease symptoms. Yet, approval of CBD as a product for medical purposes remains restricted, and CBD is less rigorously studied than conventional medicines, resulting in limited scientific data showing its efficacy.
CBD is an immunomodulator that possesses immunosuppressive and anti-inflammatory roles
One particularity of CBD is its mechanism of action: CBD activates with higher affinity the TRPV1 (transient receptor potential vanilloid 1) ion channel, compared to its cognate CB1 and CB2 receptors. TRPV1 is expressed by sensory peripheral pain neurons called nociceptors, and TRPV1 activation culminates in transmission of pain information to our brain. In parallel, TRPV1 activation induces the release, from the free nociceptor endings that innervate all mucosal epithelia, of the neuropeptide CGRP (calcitonin gene-related peptide), which is newly-recognized as an important neuroimmune modulator.
Previous studies directed by Yonatan GANOR, in the team ‘Mucosal entry, persistence and neuro-immune control of HIV-1 and other viruses’ at the Institut cochin in Paris, revealed that CGRP holds an unexpected anti-viral function: CGRP inhibits infection with HIV-1, by acting on epidermal antigen-presenting Langerhans cells (LCs) that reside in genital epithelia, and preventing them from transferring HIV-1 to its principal CD4 T-cell targets. The team also found that LCs express TRPV1, whose activation induces CGRP secretion.
In the present study of the team, performed by the postdoctoral fellow Dr Caio César Barbosa Bomfim and published in Mucosal Immunology, the scientists investigated whether CBD could be useful against HIV-1, potentially by activating TRPV1 and inducing release of CGRP with protective roles. The scientists systemically investigated the effects of CBD on the different types of mucosal immune cells that HIV-1 targets: LCs, dendritic cells (DCs), macrophages, and CD4 T-cells. The results were impressive: CBD was found to activate TRPV1 and inhibit HIV-1 infection of all four cell types.
The mechanisms, however, were different.
CBD inhibited HIV-1 transfer from LCs to CD4 T-cells, and HIV-1 direct infection of macrophages, in mechanisms that involved CGRP. CBD also inhibited HIV-1 transfer from DCs to CD4 T-cells, and HIV-1 direct infection of CD4 T-cells, but these mechanisms were independent of CGRP. These in-vitro experiments were complemented by demonstrating that CBD controls HIV-1 transmission ex-vivo. When inner foreskin tissue explants were pre-treated with CBD, and then infected with HIV-1, CBD totally blocked formation of LC-T-cell conjugates (i.e., permitting HIV-1 transfer) and almost completely the resulting infection of CD4 T-cells.
What could be the impact of this study?
Despite the existence of preventive pre-exposure prophylaxis (PrEP) strategies, recently exemplified by the extraordinary efficacy of long-lasting injectable anti-retroviral drugs, HIV-1 remains a global public health concern. PrEP is not free of limitations, as cost, access, adherence, stigma, adverse side effects and eventual drug resistance are still important barriers. The scientists propose an alternative, which they coin as ‘CBD PrEP’, which would consist of the repositioning of commercially available CBD-containing products as novel microbicides for the purpose of clinical HIV-1 prevention. Now, additional studies should evaluate the efficacy of CBD in-vivo, for instance that of already formulated lubricants that contain CBD and that are intended for topical use during sexual intercourse (i.e., the major route of HIV-1 transmission). Even if exerting only partial protection against HIV-1 acquisition, CBD PrEP could nevertheless provide an ART-free prevention option, overcome PrEP limitation, and contribute to a global reduction in HIV-1 burden, especially in middle- and low-income countries where preventive measures are the most needed.
This study was funded by SIDACCTION.
Cannabidiol (CBD) inhibits mucosal HIV-1 transmission.
Mucosal transmission mechanisms of HIV-1 involve indirect viral transfer to CD4 T-cells from Langerhans cells (LCs) or dendritic cells (DCs), and direct infection of macrophages or CD4 T-cells. All these four human mucosal cell types express the CGRP receptor, TRPV1 and CB1/2 receptors, as shown in the present study and in previous work of the team. In LCs (1), CBD activates TRPV1, resulting in secretion of CGRP that subsequently inhibits HIV-1 transfer from LCs to CD4 T-cells. In macrophages (2), CBD inhibits direct HIV-1 infection by activating TRPV1 and inducing secretion of CGRP with anti-HIV-1 effects, as well as by activating the CB2 receptor. In DCs (3), and in CD4 T-cells (4), CBD activates TRPV1 and inhibits HIV-1 transfer from DCs to CD4 T-cells and direct infection of CD4 T-cells, in mechanisms that are CGRP-independent.
Publication
Barbosa Bomfim CC, Génin H, Mariotton J, Matias I, Cota D, Barry Delongchamps N, Zerbib M, Bomsel M, Ganor Y. Cannabidiol prevents mucosal HIV-1 transmission by targeting Langerhans cells, dendritic cells, macrophages and T-cells. Mucosal Immunol. 2026.
