Neuroprotective Effects of Delta-9-Tetrahydrocannabinol in a Marmoset Parkinson Model

Sanneke A. van Vliet*, 1, 2, Raymond A. Vanwersch1, Marjan J. Jongsma1, Jan van der Gugten2, Berend Olivier 2, 3, Ingrid H. Philippens1
1 Department of Diagnosis and Therapy, TNO Defence, Security and Safety, 2288 GJ Rijswijk, The Netherlands.
2 Department of Psychopharmacology, Utrecht Institute of Pharmaceutical Sciences and Rudolf Magnus Institute of Neurosciences, Utrecht University, Utrecht, The Netherlands
3 Department of Psychiatry, Yale University School of Medicine, New Haven, USA

© 2007 van Vliet et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Department of Diagnosis and Therapy, TNO Defence, Security and Safety, 2288 GJ Rijswijk, The Netherlands; Tel: +31 651299652; Fax: +31 152843963; E-mail:,


The present medication in Parkinson’s disease (PD) is unable to stop or slow down the progression of the disease. Therefore pharmacological intervention at crucial steps in the neuronal cell death processes would be a better strategy. Cannabinoids are potent neuroprotective compounds in models of oxidative stress and excitotoxicity and offer potential protection in models of PD. Therefore the present study determines the neuroprotective effects of 􀀁9- tetrahydrocannabinol (􀀁9-THC) in the marmoset 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model on behavior and pathology. Twelve marmoset monkeys were treated with a total cumulative dose of 6 mg/kg MPTP in 9 days. Seven of these animals received simultaneously a daily oral dose of 􀀁9-THC (4 mg/kg) and five animals received simultaneously vehicle for 27 days. The parkinsonian symptoms were observed daily and locomotor activity and hand-eye coordination were tested once a week during the experimental period. Postmortem, dopamine levels in the striatum were analyzed and tyrosine hydroxylase immunohistochemistry was applied to determine viable dopaminergic neurons in the substantia nigra. 􀀁9-THC has no protective effects on any parameter. These negative results might be related to the severity of the cell death induction by MPTP in relation to the low dose of 􀀁9-THC used in this Parkinson model.