Table 2.
Pre-clinical studies investigating the effects of CBD on movement disorders.
| Model | Main findings | References |
|---|---|---|
| Hamster model of idiopathic paroxysmal dystonia | The higher dose of CBD shows a trend to delay the progression of dystonia. | Richter and Loscher, 2002 |
| PC12 cells expressing mutated huntingtin | CBD and the other three cannabinoid compounds tested—Δ8-THC, Δ9-THC, and cannabinol—show 51–84% protection against the huntingtin-induced cell death. These protective effects seem to be independent of CB1 receptors. | Aiken et al., 2004 |
| Rats lesioned by the toxin 6-OHDA | Treatment with CBD for 2 weeks subsequent to lesion by the toxin 6-OHDA prevents the 6-OHDA-induced depletion of dopamine and decrease in tyrosine hydroxylase activity in caudate-putamen. | Lastres-Becker et al., 2005 |
| Rats lesioned by the toxin 6-OHDA | Treatment with CBD for 2 weeks subsequent to lesion by 6-OHDA prevents the 6-OHDA-induced depletion of dopamine and decrease in tyrosine hydroxylase activity in caudate-putamen. CBD promoted upregulation of mRNA levels for the antioxidant enzyme Cu,Zn-superoxide dismutase. These protective effects do not seem to depend on activation of CB1 receptors. | Garcia-Arencibia et al., 2007 |
| Rats treated with 3-nitropropionic acid (3-NP) | Sub-chronic administration of 3-NP reduces GABA contents, levels of mRNA for several markers of striatal GABAergic neurons projections, and the levels of mRNA for the antioxidant enzymes superoxide dismutase-1 (SOD-1) and−2 (SOD-2). CBD reverses or attenuates the 3-NP-induced alterations. CBD's neuroprotective effects are not blocked by antagonists of the CB1, TRPV1 or A2A receptors. | Sagredo et al., 2007 |
| Rats lesioned by the toxin 6-OHDA | Treatment with CBD for 2 weeks subsequent to lesion by 6-OHDA prevents the 6-OHDA-induced decrease in tyrosine hydroxylase immunostaining, as well as enhanced microglial activation in the substantia nigra. | Garcia et al., 2011 |
| Rats treated with 3-nitropropionic acid (3-NP) or malonate | Sub-chronic administration of 3-NP reduces GABA contents, diminishes the number of Nissl-stained neurons, down-regulates the expression of CB1 receptor and IGF-1, up-regulates the expression of calpain, and reduces the expression of superoxide dismutase-1 (SOD-1). Sativex (CBD and Δ9-THC in an approximately 1:1 ratio) attenuates all the 3-NP-induced alterations. This effect is not blocked by antagonists of CB1 or CB2 receptors. In addition, rats treated with malonate display increased expression of the iNOS gene, reversed by the administration of Sativex. | Sagredo et al., 2011 |
| Rats treated with malonate | Malonate increases edema, decreases the number of surviving cells, enhances the number of degenerating cells, induces strong glial activation, and increases the expression of the inflammatory markers iNOS and IGF-1. Sativex-like combination attenuates all malonate-induced alterations. Sativex effect seems to depend on both CB1 and CB2 receptors. | Valdeolivas et al., 2012 |
| Mice injected with cataleptic agents | Pre-treatment with CBD dose-dependently attenuates the increase in catalepsy behavior induced by haloperidol, L-nitro-N-arginine or WIN 55,212-2. CBD's anticataleptic effect is prevented by the administration of WAY100635 (antagonist of 5-HT1A receptors). | Gomes et al., 2013 |
| PC12 cells treated with the toxin MPP+ | CBD increases cell viability and prevents the MPP+-induced increase in caspase-3 activation and decrease in levels of NGF. CBD treatment also induces cell differentiation even in the presence of MPP+. CBD's effects on neuritogenesis seem to depend on trkA receptors. | Santos et al., 2015 |
| Mice treated with L-DOPA | CBD, when administered with capsazepine, an antagonist of TRPV1 receptors, decreases L-DOPA-induced dyskinesia. These effects are blocked by antagonists of CB1 and PPARγ receptors. Treatment with capsazepine and CBD also decreases the expression of inflammatory markers (COX-2 and NFkB). | Dos-Santos-Pereira et al., 2016 |
| Rats injected with the cataleptic and dyskinesia-inducing agent reserpine | Repeated administration of reserpine induces catalepsy, hypolocomotion, oral dyskinesia and impairment in the discriminative avoidance memory task. Concomitant treatment with CBD prevents the increase in catalepsy behavior, the oral dyskinesia and the memory deficit. | Peres et al., 2016 |
| Mice injected with the cataleptic agent haloperidol | CBD prevents haloperidol-induced catalepsy and increase in c-Fos protein expression in the dorsolateral striatum. CBD also reverses the increase in catalepsy behavior induced by haloperidol. These CBD effects are prevented by the administration of WAY100635 (antagonist of 5-HT1A receptors). CBD's anticataleptic effect is also observed when CBD is injected into the dorsal striatum. | Sonego et al., 2016 |
| R6/2 mice (transgenic mouse models of HD) | Treatment with Sativex-like combination (from 4th to 12th weeks after birth) attenuated the R6/2 mice increased clasping behavior (that reflects dystonia) and reduced metabolic activity in basal ganglia. Sativex also reversed some of animals' alterations in markers of brain integrity, but not the deterioration in rotarod performance. | Valdeolivas et al., 2017 |
Δ8-THC, Δ8-tetrahydrocannabinol; Δ9-THC, Δ9-tetrahydrocannabinol; 3-NP, 3-nitropropionic acid; 6-OHDA, 6-hydroxydopamine; CBD, cannabidiol; HD, Huntington's disease; IGF-1, insulin growth factor 1; iNOS, inducible nitric oxide synthase; MPP+, 1-methyl-4-phenylpyridinium; NGF, nerve growth factor; PD, Parkinson's disease; SOD, superoxide dismutase.