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Author Topic: Can cannabis prevent drug-induced parkinsonism?  (Read 2187 times)

Offline tkadm30

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Can cannabis prevent drug-induced parkinsonism?
« on: 08/02/2016 14:26:33 »
The antipsychotic aripiprazole (Abilify) upregulates the DRD2 gene, a biomarker for PD etiology.

http://www.ncbi.nlm.nih.gov/pubmed/22507762

Can BDNF upregulation by cannabinoids prevent drug-induced parkinsonism (DIP) through CB1 receptor expression ?

This hypothesis would support the theory that medical cannabis can be used to treat Parkinson disease induced by partial agonists of the DRD2 receptor.  In the same time, very little is known on the pathology of DIP: Further research should investigate the role of monoamine oxidase inhibitors in the treatment of DIP. The mecanism of DIP by antipsychotics should be clarified.

https://en.wikipedia.org/wiki/Dopamine_receptor_D2

http://www.ncbi.nlm.nih.gov/pubmed/19853725
« Last Edit: 11/02/2016 10:02:51 by chris »


 

Offline exothermic

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Re: How cannabis can prevent drug-induced parkinsonism?
« Reply #1 on: 09/02/2016 01:41:38 »
I'm pretty sure the primary biological targets for enhancing BDNF-expression would be increased intracellular Ca2+ influx and/or AMPA-receptor-activation. Chronic cannabinoid-administration would likely have negligible impact on serum concentrations of BDNF [let alone enhanced expression] but that's just my opinion.

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Offline tkadm30

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Re: How cannabis can prevent drug-induced parkinsonism?
« Reply #2 on: 09/02/2016 12:01:48 »
I'm pretty sure the primary biological targets for enhancing BDNF-expression would be increased intracellular Ca2+ influx and/or AMPA-receptor-activation. Chronic cannabinoid-administration would likely have negligible impact on serum concentrations of BDNF [let alone enhanced expression] but that's just my opinion.

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Welcome to the forum exothermic. :)

I agree. Docosahexaenoic acid (DHA) may upregulate BDNF levels without cannabinoid administration. DHA is neuroprotective as well. Activation of CB1 receptors by THC may probably affect intracellular delivery of DHA to neurons.

Whether a dopamine D2 partial agonist is neuroprotective or neurotoxic is contraversial. I propose endocannabinoids can exert neuroprotection on dopaminergic neurons, preventing motor side-effects associated with DIP.

http://journal.frontiersin.org/article/10.3389/fphar.2012.00110/full
 

Offline exothermic

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Re: How cannabis can prevent drug-induced parkinsonism?
« Reply #3 on: 09/02/2016 22:56:06 »
Thank you.

I guess what I'm saying is that I'm not so sure BDNF can be effectively targeted/upregulated via OTC suppplements, as BDNF-expression is tightly regulated by neuronal activity, through Ca2+-dependent mechanisms.

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Offline tkadm30

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Re: How cannabis can prevent drug-induced parkinsonism?
« Reply #4 on: 10/02/2016 12:23:29 »
Research confirmed that DHA supplementation can improve synaptic plasticity and increase endogenous BDNF levels in plasma:

"We found that the DHA-enriched diet significantly increased spatial learning ability, and these effects were enhanced by exercise. The DHA-enriched diet increased levels of pro-BDNF and mature BDNF, whereas the additional application of exercise boosted the levels of both."

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3208643/

In addition, atypical antipsychotics may increase striatal dopamine releases and desensitization over long-term period. Hence, dopamine disinhibition might contribute to glutamate-induced excitoxicity.

http://www.nature.com/cddis/journal/v4/n1/full/cddis2012194a.html

Thus, it appears to me that endocannabinoid-like compounds (DHA) can prevent antipsychotic-induced dopamine desensitization and exert neuroprotective effects in the striatum and subthalamic nucleus.

http://www.ncbi.nlm.nih.gov/pubmed/15189766
 

Offline exothermic

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Re: How cannabis can prevent drug-induced parkinsonism?
« Reply #5 on: 11/02/2016 08:47:30 »
"Research confirmed that DHA supplementation can improve synaptic plasticity and increase endogenous BDNF levels in plasma" "We found that the DHA-enriched diet significantly increased spatial learning ability, and these effects were enhanced by exercise. The DHA-enriched diet increased levels of pro-BDNF and mature BDNF, whereas the additional application of exercise boosted the levels of both."

Yes however, is the objective to temporarily elevate plasma concentrations of BDNF - or is it to actually enhance BDNF-mediated signalling?

Keep in mind that BDNF-dysregulation is common in many neurodegenerative diseases, including PD where BDNF/NGF levels are already elevated in cerebrospinal fluid [Nagatsu et al., 2000].

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Offline tkadm30

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Re: Can cannabis prevent drug-induced parkinsonism?
« Reply #6 on: 11/02/2016 12:12:19 »
Yes however, is the objective to temporarily elevate plasma concentrations of BDNF - or is it to actually enhance BDNF-mediated signalling?

The objective is to prevent extrapyramidal symptoms induced by dopamine partial agonists such as aripiprazole.

Enhancing BDNF-mediated signaling to protect dopaminergic neurons from disinhibition may require retinoic acid stimulation. 

http://www.ncbi.nlm.nih.gov/pubmed/19457078

In addition, could endocannabinoids enhance BDNF-mediated signaling through PPAR-gamma and retinoic acid (RAR) receptor activation? This strategy would also imply that cannabis can modulate BDNF levels and increase neuroprotection of dopaminergic neurons via PPAR-gamma transactivation.

http://www.ncbi.nlm.nih.gov/pubmed/23469878
 

Offline exothermic

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Re: Can cannabis prevent drug-induced parkinsonism?
« Reply #7 on: 12/02/2016 09:41:43 »
Enhancing BDNF-mediated signaling to protect dopaminergic neurons from disinhibition may require retinoic acid stimulation.  ncbi.nlm.nih.gov/pubmed/19457078
 


From the study: "the neuroprotective effect of Am80 was suppressed by a TrkB inhibitor"

I'm fairly certain that enhancing BDNF-mediated signaling would require a change in surface charge density at the neurotrophin receptor interface - thus upregulating BDNF-induced TrkB phosphorylation. Hence the reason I questioned merely elevating plasma concentrations.

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Offline tkadm30

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Re: Can cannabis prevent drug-induced parkinsonism?
« Reply #8 on: 18/02/2016 19:39:08 »
Endocannabinoids regulate interneuron migration and morphogenesis by transactivating the TrkB receptor.

"We find that Src kinase-dependent TrkB receptor transactivation mediates endocannabinoid (eCB)-induced chemotaxis in the absence of BDNF. Simultaneously, eCBs suppress the BDNF-dependent morphogenesis of interneurons, and this suppression is abolished by Src kinase inhibition in vitro."

http://www.ncbi.nlm.nih.gov/pubmed/16357196

This looks like a cool paper!   :)



« Last Edit: 18/02/2016 19:41:39 by tkadm30 »
 

Offline tkadm30

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Re: Can cannabis prevent drug-induced parkinsonism?
« Reply #9 on: 19/02/2016 07:46:11 »
Deficient Dopamine D2 Receptor Function Causes Renal Inflammation Independently of High Blood Pressure

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3375266/

"Dopamine synthesized in the kidney is necessary for the maintenance of normal blood pressure and renal function [1]. The disruption of any of the dopamine receptor subtype genes in mice produces receptor subtype-specific hypertension [2]. "

Dopaminergic hypofunction may cause renal inflammation and weight gain: Is nocturnal hypertension an evidence of dopaminergic dysregulation or DIP ?

Blood pressure fluctuation and hypertension in patients with Parkinson's disease

"Among various autonomic dysfunctions in PD, blood pressure (BP) abnormalities such as orthostatic hypotension (Gross et al. 1972; Goldstein et al. 2005; Ziemssen and Reichmann 2010; Sharabi and Goldstein 2011), postprandial hypotension (Ejaz et al. 2006; Luciano et al. 2010), and nocturnal hypertension (Ejaz et al. 2006; Ziemssen and Reichmann 2010; Sharabi and Goldstein 2011; Sommer et al. 2011) are known"
 
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3868175/   
 

Offline tkadm30

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Re: Can cannabis prevent drug-induced parkinsonism?
« Reply #10 on: 19/02/2016 10:44:32 »
"A putative CB1/BDNF connection might be particularly relevant in the striatum, and influence their related motor disorders (e.g., Huntingtonís disease (HD) and Parkinsonís disease), as, for example, (1) the CB1 receptor is highly expressed in medium-sized spiny neurons (MSNs), the cells that constitute ~90% of total striatal neurons, and plays a key role in the control of motor behavior by basal ganglia circuitry;"

I believe cannabis can prevent drug-induced parkinsonism through neuroprotection of striatal neurons.

http://www.nature.com/cdd/journal/v22/n10/full/cdd201511a.html


« Last Edit: 19/02/2016 10:55:45 by tkadm30 »
 

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Re: Can cannabis prevent drug-induced parkinsonism?
« Reply #10 on: 19/02/2016 10:44:32 »

 

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