Table 2.
Preclinical Neuroprotective Studies of Cannabinoids
| Movement disorder | Model | Results | Reference |
|---|---|---|---|
| Parkinson’s disease | Human neuroblastoma cells (SH-SY5Y) exposed to several PD-relevant toxins (MPP, lactacystin and paraquat) | THC was neuroprotective. Neuroprotection was not blocked by CB1 antagonist (AM251). WIN 55, 212-2, nabilone, and CBD were not neuroprotective. Peroxisome-proliferator-activated receptors (PPAR) appears critical to neuroprotective effects. | 24 |
| Neuroblastoma cells | HU-210 (CB1 and CB2 receptor agonist), HU-211 (NMDA antagonist), cannabidiol, or 7-hydroxy- cannabidiol were not neuroprotective. | 119 | |
| PC12 dopaminergic neuronal cells with proteasomal synthase inhibitor exposure. | WIN55,212-2 was neuroprotective and countered accumulation of alpha-synuclein and parkin. | 120 | |
| Paraquat exposed Drosophila melanogaster | CP55,940 (CB1 and CB2 receptor agonist) increased survival when given prior to paraquat exposure and rescued the motor phenotype after exposure. | 22 | |
| 20 | 6-hydroxydopamine rats | UCM707 (selective AEA reuptake inhibitor) did not provide neuroprotection. AM404 (AEA reuptake inhibitor with additional antioxidant effects) did provide neuroprotection. | 67 |
| 6-hydroxydopamine rats | ACEA (selective CB1 receptor agonist), UCM707 (AEA transport inhibitor), and WIN55,212-2 did not reverse neurodegeneration. HU-308 (selective CB2 receptor agonist) produced slight recovery. AM404 (AEA transport inhibitor with antioxidant properties) and CBD were neuroprotective. | 21 | |
| 6-hydroxydopamine rats; lipopolysaccharide (LPS) lesioned mice | D9-THCV and CBD are neuroprotective in rats, independent of CB2 receptor function. D9-THCV and HU-308 (selective CB2 agonist) attenuated neurodegeneration in mice model and CB2 receptor deficient mice were mover vulnerable to LPS lesion. | 118 | |
| 6-hydroxydopamine rats; 6-hydroxydopamine exposed mouse cerebellar granule cells | THC and CBD reduced in vivo neurodegeneration. HU-210 (CB1 and CB2 receptor agonist) increased cell survival, particularly when glia were included in culture. | 20 | |
| MPTP knockout mice including CB1 and CB2 receptor knockouts | WIN55,212-2 and JWH015 (CB2 receptor agonist) were neuroprotective. Effects were reversed by JTE907 (CB2 receptor antagonist), unchanged in CB1 knockouts and exacerbated in CB2 knockouts. Effects may be mediated by reduced microglia activation. | 121 | |
| Huntington’s disease | Pheochromocytoma cells expressing mutant huntintgin | HU210 (CB1 and CB2 receptor agonist) had small but significant effect on cell survival including cAMP and extracellular signal-reulated kinase (ERK) mechanisms, but also had potentially toxic downstream effects including increased huntingtin aggregation. | 126 |
| Malonate rats | UCM707 (AEA transport inhibitor) did not provide neuroprotection in malonate animals | 67 | |
| Malonate rats | THC and SR141716A (selective CB1 receptor antagonist) exacerbated neurotoxicity. | 28 | |
| Malonate rats | THC/CBD compound was neuroprotective. SR141716 (selective CB1 receptor antagonist) and AM630 (selective CB2 receptor antagonist) both attenuated neuroprotective effects. | 127 | |
| Quinolinic acid rats | WIN55,212-2 (CB1 and CB2 receptor agonist) exerted neuroprotective effects and reduced extracellular glutamate. AM-251 (CB1 receptor antagonist) reversed WIN55,212-2 effects. | 124 | |
| 3NP rats | 3NP toxicity was associated with CB1 receptor reduction and THC was neuroprotective. | 122 | |
| 3NP rats | CBD, but not ACEA (CB1 receptor agonist) or HU-308 (selective CB2 receptor agonist), were neuroprotective. Rimonabant (SR141716A; selective CB1 receptor antagonist), capsazepine (TRPV1 antagonist) and MSX-3 (adenosine 2A antagonist) did not reverse effects of CBD. | 145 | |
| Malonate mice including CB2 receptor knockout | HU-308 (selective CB2 receptor agonist) was neuroprotective and reduced proinflammatory markers (TNF-alpha). Effects were reversed by SR144528 (selective CB2 receptor antagonist). CBD and ACEA (CB1 and CB2 receptor agonist) were not neuroprotective. | 125 | |
| Mice expressing human mutant huntingtin or quinolinic acid exposure including CB2 receptor knockout mice | CB2 knockouts had increased microglial activation and reduced lifespan with mutant Huntington and quinolinic acid administration. HU-308 (selective CB2 receptor agonist) reduced quinolinic acid neurotoxicity including reduced microglial activation. | 123 |
Abbreviations: 3NP: 3-Nitropropionic acid, CB1: cannabinoid receptor type 1, CB2: cannabinoid receptor type 2, CBD: cannabidiol, MPTP: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxin, PD: Parkinson’s Disease, THC: Δ9-Tetrahydrocannabinol