Dynamic changes of anandamide in the cerebrospinal fluid of Parkinson's disease patients

Abstract

A correct balance between endocannabinoid and dopamine-dependent systems is believed to underlie physiological motor control. We measured the levels of the endocannabinoid anandamide in the cerebrospinal fluid of Parkinson's disease (PD) patients. Subjects were divided into three groups: newly diagnosed de novo patients, subjects undergoing drug withdrawal, and patients under pharmacological therapy. These groups were compared to age-matched control subjects. Anandamide levels in untreated patients were more than doubled as compared to controls. However, chronic dopaminergic replacement restored control anandamide levels. Abnormal anandamide increase might reflect a compensatory mechanism occurring in course of PD, aimed at normalizing dopamine depletion.

The Pharmacology of l-DOPA-Induced Dyskinesia in Parkinson’s Disease

“…The mechanism(s), whereby elevating anandamide levels alleviates LID, is presently unknown, but the mechanisms speculated above for CB 1 agonists might well play a role. The antidyskinetic potential of FAAH inhibitors has not been explored in the clinic yet, but in agreement with a potential antidyskinetic benefit of elevating anandamide, a recent study that measured CSF levels of anandamide found decreased levels in PD patients treated with either L-DOPA or dopamine agonists compared with de novo PD patients or with patients with long-standing PD who underwent a medication washout (Pisani et al, 2010). Unfortunately, the dyskinetic status was not mentioned in the study nor was the time of last drug administration.…”

Upregulation of the cannabinoid CB2 receptor in environmental and viral inflammation-driven rat models of Parkinson's disease

“…Specifically, while rotenone infusion led to an increase in the striatal levels of anandamide, Poly (I:C) led to an increase in the striatal levels of 2-AG. Increased anandamide levels have been reported in the brains of PD patients at post mortem (Pisani et al, 2005, Pisani et al, 2010, while increased levels of 2-AG have also been observed in the brain in response to traumatic injury (Panikashvili et al, 2001). As mentioned above, these changes have been suggested to reflect a compensatory anti-inflammatory and neuroprotective response of the endocannabinoid system after brain injury (reviewed in Burstein andZurier, 2009, Scotter et al, 2010).…”

Fatty acid amide hydrolase inhibition for the symptomatic relief of Parkinson’s disease

“…et al, 2002). Significantly, DA-replacement therapy returns the elevated AEA levels to control levels in PD patients (Pisani et al, 2010). Regardless of whether these changes contribute to movement suppression or are compensatory mechanisms to counterbalance DA depletion, it is clear that the ECS is affected in parkinsonian conditions and its modulation is a promising means to improve PD motor symptoms and/or PD-related neurodegeneration.…”