Skip to main content
. Author manuscript; available in PMC: 2022 Apr 17.
Published in final edited form as: Neurosci Lett. 2021 Feb 12;750:135717. doi: 10.1016/j.neulet.2021.135717

Table 3.

Preclinical in vitro findings

Major Effects Species Sample HIV Pathogen ART Target Ligand / Antibody Effect Receptor Involved Reference
Neuronal activity Rat Hippocampal neurons Tat1–86 (clade B) No Effects of Tat on eCB system WIN55,212–2, 2-AG, JZL184, Δ9-THC Tat ↓ DSE
2-AG ↓ EPSCs
JZL184 did not affect 2-AG mediated EPSCs
WIN55,212–2 did not affect EPSC
Δ9-THC ↓ EPSC		 CB1R [241]
Neuronal damage and neuroinflammation Mouse PFC neuronal cultures Tat1–86 (clade B) No FAAH PF3845 ↑ Neuronal survival
↓ [Ca2+]i
↑ Dendritic volume
↑ AEA, PEA		 CB1R [100]
Mouse PFC neuronal cultures Tat1–86 (clade B) No Neurons AEA, 2-AG ↑ Neuronal survival
↓ [Ca2+]i
↓ Dendritic injury
↓ sEPSCs		 CB1R [244]
Human Mesencephalic neuronal/glial culture gp120LAV/IIIB (clade B) No Dopaminergic neurons WIN55,212–2 ↓ Neuronal damage
↓ Microglial damage
↓ Superoxide production
↓ Chemokine and cytokine production		 CB2R [105]
Human Primary Müller cell culture Tat (clade B) No Müller glia AEA, 2-AG AEA and 2-AG:
Suppress Müller cell activation by ↓ inflammatory cytokines
Control Tat-induced proinflammatory cytokines through MAPK phosphorylation
Inhibit NF-KB signalosome
AEA induces MKP- independent of MEK necessary for ↑ anti-inflammatory and ↓ pro-inflammatory cytokines		 CB1R, CB2R [129]
Human Primary Müller cell culture Tat (clade B) and Tat (clade C) No Müller glia AEA HIV-1 clade Tat B and C act differently
Tat B suppresses through MKP-1 and Tat C through MEK-1
↑ PBMC attachment		 CB1R, CB2R [128]
GABA Mouse Mouse brain slices Tat1–86 (clade B) No GABA WIN55,212–2, AEA AEA ↓ GABAergic neurotransmission (mIPSCs) in PFC CB1R [243]
Cyto / Neurotoxicity Rat C6 glioma cells Tat1–86 No NO synthase WIN55,212–2, AEA ↓ Cytotoxicity CB1R [74]
Human and murine Human and murine NPCs gp120IIIB (X4 strain) and gp120Ba-L (R5 strain) No CB2R AM1241 ↓ Neurotoxicity and apoptosis
↑ Differentiation of NPCs to neuronal cells
↑ Neurogenesis in vivo 		CB2R [14]
Synapse loss and neuroinflammation Rat Primary neuronal cultures gp120IIIB No MAGL JZL184 ↓ Synapse loss
↓ Prostaglandins signaling
Blocks potentiation of NMDARs		 CB2R [245]
Rat Hippocampal neuronal culture gp120IIIB No Synapse WIN55,212–2 Inhibits synapse loss
Blocks IL-1β release in microglia		 CB2R [122]
Cell migratory and/or adhesion response Human Leukemic monocyte lymphoma cell line Tat1–86 No Migration of U937 towards Tat Δ9-THC, CP55,940, O-2137 ↓ Migration of U937 microphage-like cells towards Tat CB2R [191]
Human Leukemic monocyte lymphoma cell line Tat1–86 Tat enhanced monocyte-like cell adhesion Δ9-THC, CP55,940 ↓ Attachment of U937 cells to ECM proteins by altering b-integrin expression and distribution of polymerized actin CB2R [192]
Mouse BV-2 microglial-like cells Tat1–86 No Migration of BV-2 Δ9-THC, CP55,940, 2-AG, ↓ Migration of BV-2 cells towards Tat CB2R [78]
Inhibition of viral expression Human Microglial culture None No HIV-1 WIN55,212–2 ↓ HIV-1 viral expression CB2R [198]
Human Primary monocytes None No HIV-1 JWH133, GP1a, O-1966 ↓ Activity of HIV-1 LTR
Partially ↓ expression of HIV-1 pol 		CB2R [193]
Human HIV-1 infected CD4+ lymphocyte and microglial cultures None No HIV-1 WIN55,212–2 ↓ Viral expression in both CD4+ lymphocyte and microglial cultures [186]
HIV infection Human CD4+ T cells HIVNL-GI No CD4+ T cells JWH-133, JWH-150, AM630 CB2R activation in CD4+ cells inhibit actin reorganization which prevents infection of CXCR4-tropic HIV-1 in CD4+ T cells CB2R [53]
Human Primary human monocyte cell lines None No HIV-1 Δ9-THC ↓ HIV-1 infection of macrophages
↓ Cell surface receptors CD4, CCR5, and CXCR4 which ↓ viral entry		 CB2R [237]
Human MT-2 cells None No Syncytia formation CP-55,940, Δ9-THC, WIN-55,212,2, WIN-55,212,3 Cannabimimetic drugs ↑ HIV-1 infection CB1R, CB2R [172]

Abbreviations: AEA, N-arachidonoylethanolamine; 2-AG, 2-Arachidonoylglycerol; ART, antiretroviral therapy; [Ca2+]i, intracellular calcium concentration; CB1, cannabinoid type 1 receptor; CB2, cannabinoid type 2 receptor; CBR, cannabinoid receptor; Δ9-THC, delta-9-tetrahydrocannabinol; DSE, depolarization-induced suppression of excitation; ECM, extracellular matrix; eCB, endocannabinoid system; EPSC, excitatory postsynaptic currents; FAAH, fatty acid amide hydrolase; GABA, gamma aminobutyric acid; LTR, long terminal repeat; MAGL, monoacylglycerol lipase; MAPK, mitogen-activated protein kinase; MEK, mitogen-activated protein kinase kinase; MKP-1, mitogen-activated protein kinase phosphatase-1; NF-KB, nuclear factor kappa-light-chain-enhancer of activated B cells; NMDAR, N-Methyl-D-aspartic acid receptor; NO, nitric oxide; NPCs, neuronal progenitor cells; mIPSC, miniature inhibitory postsynaptic current; PBMC, peripheral blood mononuclear cells; PEA, palmitoylethanolamide; PFC, prefrontal cortex; sEPSC, spontaneous excitatory postsynaptic current

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.