Table 2:
Preclinical animal studies (in vivo)
| Major Effects | Species | HIV Pathogen | ART | Target | Ligand | Effect | Receptor Involved | Reference |
|---|---|---|---|---|---|---|---|---|
| Neuronal activity | Mice | HIV-1IIIB Tat1–86 | No | PF3845 | Tat(+) female mice – inhibitory control deficits, ↑ CB1R in infralimbic cortex Negative correlation between inhibitory control and infralimbic CB1R expression ↑ sEPSC in Tat(+) mice PF3845 ↓ sEPSC |
CB1R | [112] | |
| Neuroinflammation and Immune cells | Rhesus macaques | SIVmac251, encephalitis | No info | CB1R, CB2R, FAAH | Anti- CB1R & anti- CB2R antibodies | ↑ CB2R microglia, perivascular macrophages and T-lymphocytes ↑ FAAH in perivascular astrocytes and astrocytic processes |
CB1R, CB2R | [21] |
| Mouse | pVRCgp120 | No info | Immune cells | Δ9-THC | ↑ or ↓ gp120 specific T cell responses depending on magnitude of IFN-γ response | No | [40] | |
| Mouse | pVRCgp120 | No info | Immune cells | Δ9-THC | ↑ gp120 specific INF-γ and IL-2 response with gp120 derived peptide 81 Δ9-THC ↑ gp120-specific T cell activation in WT but not CB1-/- and CB2-/- mice |
CB1R, CB2R | [39] | |
| Rhesus macaques | SIV | No info | CD4+ and CD8+ T lymphocytes | Δ9-THC | Chronic administration: No difference in lymphocyte subtypes, proliferation or apoptosis ↑ T lymphocyte CXCR4 expression of both CD4+ and CD8+ cells |
No | [132] | |
| Rhesus macaques | SIVmac251 | No info | miR | Δ9-THC | No differences in plasma viral loads ↑ Striatal BDNF ↓ TNF-α mRNA expression in THC/SIV group miRs modulation |
No | [216] | |
| Neurogenesis and Neuroinflammation | Mouse | GFAP/ gp120 | No | Deletion of FAAH gene | None | ↑ Neurogenesis by ↑ expression of COX-2 and PGE-2 ↓ Astrogliosis |
No | [13] |
| Mouse | GFAP/ gp120 | No | CB2R | AM1241 | ↑ Neurogenesis in hippocampus ↓ Astrogliosis and gliogenesis |
CB2R | [14] | |
| Viral load and disease progression | Rhesus macaques | SIVmac251 | No | HIV-1 RNA levels CD4+ and CD8+ cells |
Δ9-THC | No effect on disease progression, morbidity, and mortality ↓ Plasma SIV-RNA viral load and lengthened survival ↓ Classic markers of SIV disease |
No | [161] |
| Rhesus macaques | SIVmac251 | No | Effect of chronic Δ9-THC on viral load and inflammation | Δ9-THC | In lymph nodes and spleen: ↓ Viral replication ↓ Viral gag RNA ↓ INF-γ and IL-6 |
No | [160] | |
| Rhesus macaques | SIVmac251 | No | Effect of chronic Δ9-THC on plasma viral load | Δ9-THC | Tolerance to disruptive effects of Δ9-THC ↓ CB1R and CB2R levels in the hippocampus No effect on viral load in the plasma, CSF or brain tissue ↓ Neuropathology and opportunistic infections Lower expression of inflammatory cytokine MCP-1 |
No | [239] | |
| Mice (huPBL-SCID) | HIV-1NL4–3 | No | Effect of Δ9-THC on HIV-1 progression | Δ9-THC | ↑ HIV-infected peripheral blood leukocytes 50-fold ↑ viral load Upregulation of CCR5 and CXCR4 |
No | [203] | |
| Mice (huPBL/HIVE) | HIV-1ADA | No | Effect of CB2R agonist | Gp1a | ↑ CB2R expression in perivascular microglial cells and lymphocytes Gp1a ↓ infiltration of human cells in the mouse brain and HLA DQ activation Gp1a ↓ CCR5 expression on human cells in spleen ↑ Fas ligand expression |
CB2R | [85] | |
| Rhesus macaques | SIVmac251 | No | Viral load, CD4+ and CD8+ cells, IgE+ B cells | Δ9-THC | No difference in plasma viral load ↓ CD4+/CD8+ ratio ↓ IgE+ B cells |
No | [234] | |
| BBB impairment | HBMEC and human astrocyte cocultures (in vitro), mouse (in vivo) | gp120MN | No | TJ ZO-1, Claudin-5 expression | CP55,940, ACEA, URB597 |
In vitro – CP55,940 and ACEA prevented BBB permeability and prevented ZO-1 and claudin-5 downregulation in HBMEC In vivo – ACAE inhibited BBB permeability and prevented ZO-1 and claudin downregulation |
CB1R | [140] |
| Nociception | Rat | gp120MN | No | FAAH | URB597, PF3845 | ↓ Nociception in rat HIV neuropathy model ↓ Cold and tactile allodynia |
CB1R, CB2R | [167] |
| Rat | gp120IIIB | No info | None | WIN55,212–2, AMD3100 | ↓ Analgesic effectiveness AMD3100 restores the analgesic effects of WIN55,212–2 |
No | [180] |
Abbreviations: BBB, blood-brain barrier; BDNF, brain derived neurotropic factor; CB1R, cannabinoid type 1 receptor; CB2R, cannabinoid type 2 receptor; CBR, cannabinoid receptor; COX-2, cyclooxygenase-2; CSF, cerebrospinal fluid; Δ9-THC, delta-9-tetrahydrocannabinol; FAAH, fatty acid amide hydrolase; GFAP, glial fibrillary acidic protein; HBMEC, human brain microvascular endothelial cells; IFN-γ, Interferon gamma; IgE, immunoglobulin E; IL-2, interleukin 2; ; IL-6, interleukin 6; miR, microRNA; PGE-2, prostaglandin E2; SIV, simian immunodeficiency virus; sEPSC, spontaneous excitatory postsynaptic current; TJ ZO-1, tight junction zonula occludens-1; TNF-α, tumor necrosis factor alpha; WT, wild-type; ZO-1, zonula occludens-1
Criteria for exclusion from this Table: (1) Studies on cannabinoids and HIV effects not directly related to the central nervous system. (2) Studies on the effects of cannabinoids on other diseases/disease pathogens.