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] |