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Table 1 Summary of the pharmacological effects demonstrated by cannabinoids in various model of PD and other neurodegenerative diseases

From: Promising cannabinoid-based therapies for Parkinson’s disease: motor symptoms to neuroprotection

Compound Model Activity profile Ref.
Oleoylethanolamide (OEA) 6-OHDA model of PD in mice OEA reduces dyskinetic symptoms and molecular markers of dyskinesias including striatal overexpression of FosB and phosphoacetylation of histone 3 [196]
Oral Cannabinoid Extract (OCE) A Class I double-blind crossover study in dyskinetic patients OCE was ineffective for treating levodopa-induced dyskinesias in patients with PD [334]
Cannabis administration via smoking Open-label observational study in 22 PD patients Cannabis was found to improve tremor, rigidity and bradykinesia in PD patients. Also, sleep and pain scores were also improved [335]
WIN-55,212-2 L-DOPA-induced motor fluctuation model of PD WIN-55,212-2 significantly reduced AIMs to L-DOPA in 6-OHDA-lesioned rats by modulating DARPP-32 and ERK1/2 phosphorylation in striatal neurons [336]
OEA and Palmitoylethanol-amide (PEA) LPS-induced neuroinflammation in rat OEA and PEA inhibited oxidative and nitrosative stress by reducing LPS-induced NFκB expression and subsequent release of proinflammatory mediators [337]
WIN-55,212-2 and HU-210 Intranigral injection of LPS in rats WIN-55,212-2 and HU210 increased the survival of nigral neurons, inhibited activation of NADPH oxidase, ROS production and production of proinflammatory cytokines [338]
THC MPP+, lactacystin and paraquat induced neurotoxicity in SH-SY5Y cells THC exhibited neuroprotective effect against all toxins probably by activation of PPAR-γ receptors [339]
THCA, THC and CBD MPP+ induced cytotoxicity to mice mesencephalic cultures All cannabinoids exhibited anti-oxidative action. THC and THCA protected dopaminergic neurons [340]
WIN-55,212-2 L-DOPA-induced (AIMs) in the 6-OHDA injected rat WIN-55,212-2 ameliorated L- DOPA induced AIMs [341]
WIN-55,212-2 PSI-induced cytotoxicity in PC12 cells WIN-55,212-2 protects PC12 cells from PSI-induced cytotoxicity, Inhibits cytoplasmic accumulation of parkin and α-synuclein [342]
WIN-55,212-2 and HU-210 MPTP model of PD WIN-55,212-2 and HU210 increased survival of DA neurons in the SN, reduced expression of proinflammatory cytokines and improved motor function [343]
(9)-THCV Unilateral 6-OHDA lesions in rats (9)-THCV attenuated the motor inhibition [273]
(9)-THCV LPS model of PD in mice (9)-THCV decreased microglial activation and protected nigral TH neurons [273]
AM251 and HU210 Levodopa-induced dyskinesia in a rat model HU210 significantly reduced certain subtypes of AIMs while, AM251 had no effect on AIMs [344]
WIN-55,212-2 MPTP model of PD WIN-55,212-2 protected TH neurons in the SN [42]
Rimonabant Unilateral 6-OHDA lesions Rimonabant improved motor behavior [345]
JWH015 MPTP model of PD in mice JWH015 reduced MPTP-induced microglial activation [42]
Adenoviral vector enforced expression of the CB1 receptor R6/2 mouse model of HD Vector-enforced expression of CB1 receptor causes re-expression of BDNF and cures neuropathological deficits [346]
CBD 3NP model of HD in rats CBD protected striatal neuron by completely reversing 3NP-induced reductions in GABA contents and mRNA levels for SP, NSE and SOD-2 [347]
CBD β-amyloid-induced model of AD in rats with or without GW9662 Presence of GW9662 was able to significantly block protective effects of CBD on reactive gliosis and on neuronal damage. CBD also induced hippocampal neurogenesis [280]
JWH-133 AβPP/PS1 genetic model of AD JWH-133 lowered microglial activity, decreased expression of pro-inflammatory cytokines and tau hyperphosphorylation [348]
Sativex® Human tau overexpressing mice model of AD Sativex® decreased gliosis and generation of free radical in hippocampus and cortex [349]
MDA7 Aβ-induced model of AD in rats MDA7 mitigated the expression of microglia and astroglial markers, reduced the secretion of interleukin-1β, diminished the increase of CB2 receptors, promoted clearance of Aβ and restored synaptic plasticity, cognition, and memory [350]
CBG 3NP model of HD in mice CBG improved motor deficits and preserved striatal neurons. CBD also decreased reactive gliosis and upregulated antioxidant defenses [351]
HU210 PC12 cells model of HD expressing mutant huntingtin HU210 increased cell survival, by cyclic adenosine monophosphate and extracellular signal-regulated kinase mechanisms [352]
ACEA, HU-308 and CBD Malonate induced model of HD in rats Activation of CB2 receptor diminished reactive gliosis and subsequent release of proinflammatory cytokine [115]
  1. Abbreviations: DA, dopamine; THCA, Tetrahydrocannabinolic acid; CBD, cannabidiol; MPP+, 1-methyl-4-phenylpyridinium; AIMs, abnormal involuntary movements; SN, substantia nigra; 9-THCV, tetrahydrocannabivarin, THC, Tetrahydrocannabinol TH, tyrosine hydroxylase; LPS, lipopolysaccharide ; 6-OHDA, 6-hydroxydopamine; PSI, proteasome inhibitor; 3NP, 3-nitropropionic acid; HD, Huntington’s Disease; SP, substance P; NSE, neuronal-specific enolase; SOD, superoxide dismutase; AD, Alzheimer’s disease; MDA7, 1-((3-benzyl-3-methyl-2,3-dihydro-1-benzofuran-6-yl) carbonyl) piperidine; CBG, Cannabigerol.