In a brain region, the so-called striatum, that controls planning and execution of motor behaviours, researchers of the University of California at Irvine have demonstrated interactions of the endocannabinoid signalling system with the dopamine neurotransmitter system. The striatum contains a large number of CB1 cannabinoid receptors. Abnormalities in the striatal neuromodulation have been linked to diseases such as Parkinson's disease and Tourette's syndrome. Dr. A. Giuffrida and colleagues revealed a physiological mechanism by which endocannabinoids are involved in the function of striatal neurons. Their study with male rats was published in the April issue of nature neuroscience (Giuffrida et al. 1999).

The results were as followed:
1. The endocannabinoid anandamide was released by neural activity, but there was no effect on the endocannabinoids palmitylethanolamide, oleylethanolamide and 2- arachidonylglycerol. This indicates that in the striatum such a role is specific to anandamide.
2. Activation of dopamine receptors with a dopamine-2(D2)-like receptor ligand led to an eightfold stimulation of anandamide outflow. Dopamine-1(D1)-like receptor agonists had no effect.
3. The behavioural response to a systemic administration of D2- like agonists -- a biphasic motor response characterized by a transient suppression of movement followed by a longer-lasting hyperactivity -- were affected by the CB1 receptor antagonist SR141716A. The late phase was markedly potentiated by the CB1 antagonist.

The researchers concluded, that the physiological role of anandamide may be "to counter dopamine stimulation of motor activity. (...) Thus, our findings may have implications for neuropsychiatric disorders such as schizophrenia, Tourette's syndrome and Parkinson's disease and may point to novel therapeutic approaches for these conditions." It seemed that anandamide may act in the central nervous system more as a local mediator such as the prostaglandins than as a classical neuromodulator.

In a commentary Dr. David W. Self from the Division of Molecular Psychiatry at Yale University added, that this research promises "to propel anandamide from candidate status to bona fide neurotransmitter" (Self 1999). In the striatum anandamide "seems to function as a brake" that limits the behavioural response to dopamine receptor activation. This could lead to the development of drugs that block the cannabinoid receptor to enhance the therapeutic efficacy of dopamine-based treatments, and to drugs that stimulate the CB1-receptor, reducing dyskinetic movements caused by a hyperactivity of dopamine.

This hypothesis is supported by the successful use of cannabis by patients suffering from hyperkinetic movement disorders such as tremor in multiple sclerosis, Tourette's syndrome, and tardive dyskinesia due to antipsychotic medication. Dr. J. M. Brotchie from the university of Manchester, Great Britain, discussed cannabinoids as well as an adjunct to dopamine replacement to reducing the problem of dyskinesia in Parkinson's disease (Brotchie 1998).

Sources:
Giuffrida A, et al: Nature neuroscience (1999 Apr) 2(4):358-63
Self DW: Nature neuroscience (1999 Apr) 2(4):303-4
Brotchie JM: Mov Disord (1998 Nov) 13(6):871-6