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. 2024 Aug 7;25(16):8630. doi: 10.3390/ijms25168630

Table 1.

Main results from the studies with selective CB1R agonists.

Reference Cannabinoid Dosage Major Results Model Used
Crunfli et al., 2019 [52] ACEA 3 mg/kg i.p.

  • ↑ Short-term memory

  • ↑ Long-term memory

  • ↑ Cell viability

 In vitro and in vivo experiments in AD models with STZ
Moreira-Silva et al., 2018 [53] AEA 100 ng i.c.v.

  • Repair of new object recognition impairments and prevention of non-associative emotional memory disorders (NOR, EPM tests)

  • Prevention of cerebroventricular enlargement

  • Restoration of synaptophysin and syntaxin levels

 In vivo experiments in Wistar rats with STZ injection
Khavandi, Rao and Beazely, 2023 [54] AΕA 10 μΜ

  • ↑ Cell viability

  • ↓ Accumulation of Aβ42

 In vitro experiments in mouse hippocampal HT22 cells and hamster ovary CHO cells expressing human CB1R
Noladin 10 μΜ

  • ↑ Cell viability

  • ↓ Accumulation of Aβ42
OAΕ 1 μM
10 μΜ

  • ↑ Cell viability
Hosseininia et al., 2023 [55] ACPA 10 ng/0.5 μL (corticolimbic microinjection)

  • ↑ Step-through latency by ACPA, independent of injection region (CA1, CeA, mPFC)

  • ↓ MAGL expression by miR-137/let-7a

  • Elimination of amnesiac effect of STZ

 In vivo experiments in Wistar rats after i.c.v. STZ
Lentiviral particles with miR-137 or miR-let-7a 0.5 μL/rat e.o.d.
Zhang et al., 2016 [56] RVD and VD 1 nmol
2.5 nmol
5 nmol,
i.c.v./i.p.

  • ↑ Discrimination index (NOR, OLR)

 In vivo experiments in mice infected with Aβ1-42
Zhang et al., 2021 [57]

  • Dose-dependent restoration of memory function (NOR, OLR)

 In vivo experiments in mice after i.p. scopolamine
Zhang et al., 2020a [58] VD

  • ↑ Cell viability

  • ↓ ROS, MDA

  • ↑ CAT, GPx

  • ↓ Bax, ↑ Bcl-2

 In vitro experiments on hippocampal neurons from mice infected with Aβ1-42
Zhang et al., 2023 [59] RVD

  • ↑ Cell viability

  • ↓ ROS, MDA

  • ↑ CAT, GPx

  • ↓ Bax, ↑ Bcl-2

  • Restoration of BDNF/TrkB/Akt pathway

  • ↑ Synapsin-1, PSD-95

 In vitro experiments in HT22 cells treated with scopolamine
Zhang et al., 2020b [60]

  • ↑ Cell viability

  • ↓ Phosphorylation of TAU

  • Inhibition of PKA, GSK-3β

  • Restoration of neuronal growth

 In vitro experiments in SH-SY5Y cells infected with Aβ1-42
Velikova, Doncheva and Tashev, 2020 [61] HU-210 5 μg/day i.c.v.

  • Improvement in memory

 Direct correlation of CB1R with memory function (active and PA tests) In vivo experiments in OBX rats
SR 141716A (CB1R Antagonist) 3 μg/day i.c.v.

  • Deterioration of memory

Abbreviations: Aβ: amyloid beta; ACEA: arachidonyl-2′-chloroethylamide; ACPA: arachidonylcyclopropylamide; AD: Alzheimer’s disease; AEA: anandamide; Akt: protein kinase B; Bax: Bcl-2-associated X protein; Bcl-2: B cell leukemia/lymphoma 2 protein; BDNF: brain-derived neurotrophic factor; CAT: catalase; CB1R: cannabinoid receptor 1; CeA: central amygdala; e.o.d.: every other day; EPM: elevated plus maze; GPx: glutathione peroxidase; GSK-3β: glycogen synthase kinase-3 beta; i.c.v.: intracerebroventricular; i.p.: intraperitoneally; MAGL: monoglycerol lipase; MDA: malondialdehyde; miR: microRNA; mPFC: medial prefrontal cortex; NOR: novel object recognition; OAE: O-arachidonylethanolamine; OBX: olfactory bulbectomy; OLR: object location recognition; PA: passive avoidance; PKA: protein kinase A; PSD-95: postsynaptic density protein 95; ROS: reactive oxygen species; RVD: (m)RVD-hemopressin; STZ: streptozotocin; TrkB: tropomyosin receptor kinase B; VD: (m)VD-hemopressin.