In Parkinson’s patients, microglia surrounding lesions in the substantia nigra have increased CB2 levels (Gómez-Gálvez et al., 2015). Experiments in mice showed that this increase in CB2 is neuroprotective. Thus CB2 signalling may provide a therapeutic avenue to prevent neurodegeneration in Parkinson’s.
GPR6 has been associated with Parkinson's disease (Laun & Song, 2017).
In human neuroblastoma cells, THC, but not CBD was found to be neuroprotective. Neuroprotection was mediated by PPARγ (Carroll et al., 2012).
In a rat model of Parkinson’s Disease, THCV and CBD were neuroprotective in a CB2-independent way (García et al., 2011). THCV also improved mobility in this study.
In a similar study, THC and CBD were neuroprotective via CB1 or CB2 receptors (Lastres-Becker et al., 2005).
In cultured midbrain neurons, CBD, THCA and THC had anti-oxidative properties. Moreover, THCA and THC were shown to be neuroprotective (Moldzio et al., 2012).
Similar results were obtained with 2AG, the body’s major endocannabinoid (Mounsey et al., 2015).
In a marmoset model of Parkinson’s THC improved locomotor activity (van Vliet et al., 2006).
In one study, Anandamide was found to reduce dopamine release via TRPV1 receptors (de Lago et al., 2004) suggesting their involvement in movement behaviour.
In a mouse model of Parkinson’s, OEA (at 5mg/kg) protected dopaminergic neurons from degeneration in a PPARα-dependent way (Gonzalez-Aparicio et al., 2014).
Similarly, systemic application of OEA, and to a lesser extent PEA, was found to inhibit pro-inflammatory cytokines and thus to protect against neurodegeneration (Sayd et al., 2014).
In another study, OEA reduced L-dopa-induced-dyskinesia in a TRPV1-dependent way (González-Aparicio and Moratalla, 2014).
Carroll, C.B., Zeissler, M.-L., Hanemann, C.O., and Zajicek, J.P. (2012). Δ9-tetrahydrocannabinol (Δ9-THC) exerts a direct neuroprotective effect in a human cell culture model of Parkinson’s disease. Neuropathol. Appl. Neurobiol. 38, 535–547.
García, C., Palomo-Garo, C., García-Arencibia, M., Ramos, J., Pertwee, R., and Fernández-Ruiz, J. (2011). Symptom-relieving and neuroprotective effects of the phytocannabinoid Δ9-THCV in animal models of Parkinson’s disease. Br. J. Pharmacol. 163, 1495–1506.
Gómez-Gálvez, Y., Palomo-Garo, C., Fernández-Ruiz, J., and García, C. (2015). Potential of the cannabinoid CB2 receptor as a pharmacological target against inflammation in Parkinson’s disease. Prog. Neuropsychopharmacol. Biol. Psychiatry.
González-Aparicio, R., and Moratalla, R. (2014). Oleoylethanolamide reduces L-DOPA-induced dyskinesia via TRPV1 receptor in a mouse model of Parkinson´s disease. Neurobiol. Dis. 62, 416–425.
Gonzalez-Aparicio, R., Blanco, E., Serrano, A., Pavon, F.J., Parsons, L.H., Maldonado, R., Robledo, P., Fernandez-Espejo, E., and de Fonseca, F.R. (2014). The systemic administration of oleoylethanolamide exerts neuroprotection of the nigrostriatal system in experimental Parkinsonism. Int. J. Neuropsychopharmacol. Off. Sci. J. Coll. Int. Neuropsychopharmacol. CINP 17, 455–468.
de Lago, E., de Miguel, R., Lastres-Becker, I., Ramos, J.A., and Fernández-Ruiz, J. (2004). Involvement of vanilloid-like receptors in the effects of anandamide on motor behavior and nigrostriatal dopaminergic activity: in vivo and in vitro evidence. Brain Res. 1007, 152–159.
Lastres-Becker, I., Molina-Holgado, F., Ramos, J.A., Mechoulam, R., and Fernández-Ruiz, J. (2005). cannabinoids provide neuroprotection against 6-hydroxydopamine toxicity in vivo and in vitro: relevance to Parkinson’s disease. Neurobiol. Dis. 19, 96–107.
Laun, A. S., & Song, Z.-H. (2017). GPR3 and GPR6, novel molecular targets for cannabidiol. Biochemical and Biophysical Research Communications, 490(1), 17-21. https://doi.org/10.1016/j.bbrc.2017.05.165
Moldzio, R., Pacher, T., Krewenka, C., Kranner, B., Novak, J., Duvigneau, J.C., and Rausch, W.-D. (2012). Effects of cannabinoids Δ(9)-tetrahydrocannabinol, Δ(9)-tetrahydrocannabinolic acid and cannabidiol in MPP+ affected murine mesencephalic cultures. Phytomedicine Int. J. Phytother. Phytopharm. 19, 819–824.
Mounsey, R.B., Mustafa, S., Robinson, L., Ross, R.A., Riedel, G., Pertwee, R.G., and Teismann, P. (2015). Increasing levels of the endocannabinoid 2-AG is neuroprotective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson’s disease. Exp. Neurol.
Sayd, A., Antón, M., Alén, F., Caso, J.R., Pavón, J., Leza, J.C., Rodríguez de Fonseca, F., García-Bueno, B., and Orio, L. (2014). Systemic administration of oleoylethanolamide protects from neuroinflammation and anhedonia induced by LPS in rats. Int. J. Neuropsychopharmacol. Off. Sci. J. Coll. Int. Neuropsychopharmacol. CINP 18.
van Vliet, S.A.M., Vanwersch, R.A.P., Jongsma, M.J., van der Gugten, J., Olivier, B., and Philippens, I.H.C.H.M. (2006). Neuroprotective effects of modafinil in a marmoset Parkinson model: behavioral and neurochemical aspects. Behav. Pharmacol. 17, 453–462.