Table 4.
Cannabinoid studies in animal models
| Disease model | Animal | Disease model | eCB/CB | Target/mechanism | Reference |
|---|---|---|---|---|---|
| Seizures | Rat | Pentylenetetrazole | CBD | Not determined | Jones et al., 2010 |
| Rat (neonatal) | Ouabain | THC | CB1-mediated neuroprotective effect | van der Stelt et al., 2001 | |
| Oxidative stress | Rat (postnatal to adult) | Iron overload (iron carbonyl) | CBD | Prevented loss of memory function | da Silva et al., 2018 |
| Rat | STZ-induced oxidative stress | SR141716, AM1710 | CB1 inhibition (SR141716) and/or CB2 activation (AM1710) reduced nitrative stress | Spyridakos et al., 2022 | |
| Stroke | Rat | MCAO | PEA | Neuroprotection was CB1-/VR1-independent but AM404 prevented protection | Garg et al., 2010 |
| Rat | MCAO | LLEA | Decreased cortical infarct volume and improved neurological deficit score | Garg et al., 2011 | |
| Rat | MCAO | WIN 55512-2, SR141716A | Neuroprotection elicited by CB1 agonist (WIN 55512-2), was inhibited by CB1 antagonist (SR141716A) | Nagayama et al., 1999 | |
| Rat | MCAO | BAY 38-7271 | Generated neuroprotection; decreased intracranial pressure | Mauler et al., 2003 | |
| Rat | BCCAO | URB597 | FAAH inhibition improved spatial memory and learning; prevented neuronal death | Wang et al., 2021 | |
| Inflammation | Mouse | LPS injection | CBD | Inhibited vasodilation, reduced leukocyte margination, blocked TNFα, COX-2 and iNOS upregulation, and maintained integrity of the blood-brain barrier | Ruiz-Valdepeñas et al., 2011 |
| Mouse | Human PBL/HIVE immunodeficient mice | Gp1a | Gp1a is a CB1 agonist; decreased human cell penetration into the mouse brain | Gorantla et al., 2010 | |
| Rat (neonatal) | Ouabain | THC | THC reduced astogliosis | van der Stelt et al., 2001 | |
| Rat | Borna virus infection | WIN 55,212 | Protected proliferating striatal progenitor cells, inhibition of microglia activation; augmented striatal progenitor cell proliferation/survival; increased number of proliferating oligodendrocyte progenitor cells and reduced phagocytic cells | Solbrig et al., 2010 | |
| Traumatic brain injury | Mouse | Controlled cortical impact | VCE-004.8 | Promoted neovascularization, blocked infiltrations of immune cells, and reduced neuroinflammation and inhibited neuronal death | Navarrete et al., 2022 |
| Rat | Closed concussive injury | BAY 38-7271 | Neuroprotection | Mauler et al., 2003 | |
| Rat | Closed concussive injury | HU-211 | Improved motor function in a head trauma model | Shohami et al., 1993 | |
| Multiple sclerosis | Mouse | Experimental autoimmune encephalitis (EAE) | THC & CBD | THC and CBD reduced IL-6 and IL-17, elevated immunosuppressive cytokine, IL-10; THC and CBD decrease the Th17 phenotype | Kozela et al., 2013 |
| FAAH KO mouse | Chronic mouse EAE model | Elevated eCBs | Displayed greater clinical remission compared to wild type mice | Webb et al., 2008 | |
| Mouse | Experimental allergic uveitis model | WIN 55,212, CP55,940, SR141716 | CB1 agonists elicited neuroprotection | Pryce et al., 2003 | |
| C57Bl/6 mouse | Cuprizone-induced demyelination | THC | Regeneration of oligodendrocytes, remyelination of white matter, and recovery of motor function | Aguado et al., 2021 | |
| Mouse | Chronic relapsing experimental allergic encephalomyelitis | WIN 55,212, THC, methanandamide and JWH-133 | Ameliorated both tremor and spasticity | Baker et al., 2000 | |
| Alzheimer’s disease | Mouse | CB2−/− mice | n.a. | Tau hyperphosphorylation, mitochondria dysfunction, and memory dysfunction | Wang et al., 2018 |
| Rat | Okadaic acid (OKA) induced spatial memory impairment | JWH-133 | Prevented the increase in caspase-3, Aβ, phosphorylated tau, and IL-1β in cortical and hippocampal regions | Çakır et al., 2019 | |
| Parkinson’s disease | Mouse | MPTPp | URB597 | Inhibited motor impairment via CB1/CB2 | Celorrio et al., 2016 |
| Monkey | MPTP, L-DOPA | n.a. | MPTP & L-DOPA treatments altered the expression of CB1 & 2-AG metaboloc enzymes | Rojo-Bustamante et al., 2018 | |
| AMD | Mouse | SOD1G93A mutant mice | WIN55,212-2 | WIN55,212-2 (CB1/CB2 agonist) slows disease progression | Bilsland et al., 2006 |
| Huntington’s disease | Mouse | R6/2 mouse | Nabiximols | Reduced clasping behavior | Valdeolivas et al., 2017 |
| Pain | Rat | Sciatic nerve constriction; inflammatory pain | CBD | Reduced hyperalgesic effect via TRPV1 | Costa et al., 2007 |
| Rat | Arthritis pain | CBD | Transdermal delivery of CBD reduced inflammation and pain | Hammell et al., 2016 | |
| Mouse | Neuropathic pain | CBD-NLC-gel | Nasal delivery of CBD-nano-structured lipid carrier complex | Matarazzo et al., 2020 | |
| Neuropsychiatric disorders | Mouse | Chronic stress model | CBD | Anxiolytic effects, increase in hippocampal neurogenesis | Schiavon et al., 2016 |
| Mouse | Olfactory bulbectomy model of depression | CBD | Increase in glutamate and serotonin in the ventromedial prefrontal cortex via 5HT1A inhibition | Linge et al., 2015 |
Aβ: Amyloid β; AMD: age-related macular degeneration; BCCAO: bilateral common carotid artery occlusion; CB: cannabinoid; CBD: cannabidiol; EAE: experimental autoimmune encephalitis; IL-1β: interleukin-1β; IL-10: interleukin-10; IL-17: interleukin-17; IL-6: interleukin-6; KO: knockout; L-DOPA: levodopa; LLEA: N-linoleoylethanolamine; LPS: lipopolysaccharide; MCAO: middle cerebral artery occlusion; MPTP: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; MPTPp: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and probenecid; PEA: N-palmitoylethanolamine; STZ: streptozotocin; Th17: T helper cell 17; THC: Δ9-Tetrahydro-cannabinol.