Parkinson's disease

Parkinson’s disease: cannabidiol, tetrahydrocannabinol, CB1 and CB2 receptors and anti-oxidant properties in neuroprotection 

Virginia Thornley, M.D., Neurologist, Epileptologist

March 2, 2018

Introduction

Cannabinoids are compounds part of the endocannabinoid pathways found inherent to the brain comprising of endocannabinoids, transporters and receptors. Cannabidiol is a mimetic for 2-2-arachidonyl (2-AG) and tetrahydrocannabinol is a mimetic for Anandamide (AEA). 2 receptors for cannabidiol are found in the brain CB1 mainly seen in the basal ganglia and limbic system and CB2 found in the immune system. The receptors are G-coupled and suppress adenylate.

With Parkinson’s disease, there is reduced production of dopamine in the substantia nigra which means there is less inhibitory effect on the basal ganglia resulting in increased acetylcholine from the basal ganglia which results in tremors. Cannabinoids appear to influence the neurotransmitter system within the brain and have found to be beneficial in movement disorders in the animal model.

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Mechanisms of cannabidiol and THC in Parkinson’s disease animal model

There are more CB1 receptors in brains with Parkinson’s disease and the MPTP model, likely a result of less inhibition from the dopaminergic substances and a compensatory mechanism in the brain. There are more CB1 receptors possibly as a response to the reduced dopaminergic effect (2). It was postulated that CB1 agonists may exert a neuroprotective effect against 3 toxins paraquat, MPP+, and lactasyn. However, using experimental techniques, the neuroprotection from 9THC is likely not related to the CB1 receptor. Evidence supports that the neuroprotection afforded by THC may be related to its antioxidant properties. This may be through the effects of PPARy or the peroxisome proliferator-activated receptor gamma.

Other studies propose that the neuroprotective effects of cannabidiol and THC are independent of the CB1 receptor and related to the antioxidant effects. It was found that CB2 receptor activation may slow the progression of neurodegeneration on Parkinson’s disease. CB2 receptors are found naturally in the cells but appear upregulated in diseased cells such as in Parkinson’s disease, suggesting an endogenous protective effect. It may exert effects by reducing proinflammatory responses. Activation of CB2 receptors may represent a promising role of CB2 receptors in the treatment of Parkinson’s disease (3).

Cannabidiol and clinical studies in Parkinson’s disease

In one study of 119 patients, cannabidiol was given at 75mg/day or 300mg/day. Patients were assessed using variables of motor symptoms according to the UPDRS, well-being and life quality (PDQ-39) and neuroprotective effects.

One week before the trial and in the last week of treatment participants were assessed in respect to (i) motor and general symptoms score (UPDRS); (ii) well-being and quality of life (PDQ-39); and (iii) possible neuroprotective effects (BDNF and H(1)-MRS). They found no difference in motor assessment and neuroprotection but the quality of life seemed to improve in the group taking 300mg compared with placebo(1).

 

Medical marijuana has been demonstrated to be effective in bradykinesia, tremors seen in the Parkinson’s disease. Cannabinoids have been found effective in psychosis and sleep disorders seen in Parkinson’s disease(4).

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References

  1. Chagas, et al, “Effects of cannabidiol in the treatment of patients with Parkinson’s disease: an exploratory double-blind trial,” Journal of Psychopharmacology, 2014, Nov., 28(110):1088-1098.
  2.  Carroll, et al, “9-Tetrahydrocannabinol exerts a direct neuroprotective effect in human cell culture model of Parkinson’s disease,” Neuropathology and Applied Neuropharmacology, 2012, Oct., 38(6):3535-547.
  3. Fernandez-Ruiz, et al, “Prospects of cannabinoid therapies in basal ganglia disorder,” British Journal of Pharmacology, 2011, Aug., 163 (7):1365-1378.
  4. Babyeva, et al, “Marijuana compounds: a non-conventional approach to Parkinson’s disease therapy,” Parkinson’s Disease, 2016:1279042.
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