Naked Science Forum
Life Sciences => Physiology & Medicine => Topic started by: smart on 30/07/2016 22:48:43
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Does THC administration stimulate endocannabinoid synthesis and uptake?
If so, is there any pharmacological alternatives to stimulate endogenous cannabinoid receptors
without THC?
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Does THC administration stimulate endocannabinoid synthesis and uptake?
The lesson from administering biologically active opioids and steroids is that they tend to reduce production of the body's natural equivalent, and/or reduce the sensitivity of the receptors.
This is because the body has a closed-loop control system, which tries to keep the body in chemical balance.
So I suspect that it will have the opposite effect of what you suggest.
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Does THC administration stimulate endocannabinoid synthesis and uptake?
The lesson from administering biologically active opioids and steroids is that they tend to reduce production of the body's natural equivalent, and/or reduce the sensitivity of the receptors.
This is because the body has a closed-loop control system, which tries to keep the body in chemical balance.
So I suspect that it will have the opposite effect of what you suggest.
I agree. But is not cannabinoid receptor 1 (CB1) responsible for endocannabinoid synthesis?
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The CB1 receptor is a pre-synaptic heteroreceptor that modulates neurotransmitter release when activated in a dose-dependent, stereoselective and pertussis toxin-sensitive manner.[3] The CB1 receptor is activated by cannabinoids, generated naturally inside the body (endocannabinoids) or introduced into the body as cannabis or a related synthetic compound.
https://en.wikipedia.org/wiki/Cannabinoid_receptor_type_1#Mechanism
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The lesson from administering biologically active opioids and steroids is that they tend to reduce production of the body's natural equivalent, and/or reduce the sensitivity of the receptors.
THC isn't an opioid.... or a steroid, so what exactly are you implying?
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Does THC administration stimulate endocannabinoid synthesis and uptake?
Yes.
Biochemical Pharmacology
1 November 2004, Vol.68(9):1691–1698, doi:10.1016/j.bcp.2004.07.007
On-demand activation of the endocannabinoid system in the control of neuronal excitability and epileptiform seizures.
Neurons intensively exchange information among each other using both inhibitory and excitatory neurotransmitters. However, if the balance of excitation and inhibition is perturbed, the intensity of excitatory transmission may exceed a certain threshold and epileptic seizures can occur. As the occurrence of epilepsy in the human population is about 1%, the search for therapeutic targets to alleviate seizures is warranted. Extracts of Cannabis sativa have a long history in the treatment of various neurological diseases, including epilepsy. However, cannabinoids have been reported to exert both pro- and anti-convulsive activities. The recent progress in understanding the endogenous cannabinoid system has allowed new insights into these opposing effects of cannabinoids. When excessive neuronal activity occurs, endocannabinoids are generated on demand and activate cannabinoid type 1 (CB1) receptors. Using mice lacking CB1 receptors in principal forebrain neurons in a model of epileptiform seizures, it was shown that CB1 receptors expressed on excitatory glutamatergic neurons mediate the anti-convulsive activity of endocannabinoids. Systemic activation of CB1 receptors by exogenous cannabinoids, however, are anti- or pro-convulsive, depending on the seizure model used. The pro-convulsive activity of exogenous cannabinoids might be explained by the notion that CB1 receptors expressed on inhibitory GABAergic neurons are also activated, leading to a decreased release of GABA, and to a concomitant increase in seizure susceptibility. The concept that the endogenous cannabinoid system is activated on demand suggests that a promising strategy to alleviate seizure frequency is the enhancement of endocannabinoid levels by inhibiting the cellular uptake and the degradation of these endogenous compounds.
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The lesson from administering biologically active opioids and steroids is that they tend to reduce production of the body's natural equivalent, and/or reduce the sensitivity of the receptors.
THC isn't an opioid.... or a steroid, so what exactly are you implying?
That drug abusers become dependent perhaps? It seemed obvious to me. Maybe all that THC dulls your perception.
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Did I hurl obscenities? You have already demonstrated your willingness to not only break the law by getting behind the wheel of a vehicle intoxicated but advocate it to others as long as they get the dose right. That I happen to mention it from time to time is not insulting you.
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You have already demonstrated your willingness to not only break the law by getting behind the wheel of a vehicle intoxicated but advocate it to others as long as they get the dose right.
Similar in fashion to the forum member IAMREALITY, attempting to explain anything regarding physiology or pharmacology to you is useless, because you have no background in either.... and it's blatantly/painfully obvious.
Based on your past drivel-mediated ramblings, you will simply never comprehend that THC can elicit cognitive [enhancement] in those who use it regularly.
~
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What is your mother's maiden name?
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I guess that one isn't included in the enhancement of cognition.
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Does THC administration stimulate endocannabinoid synthesis and uptake?
Yes.
Biochemical Pharmacology
1 November 2004, Vol.68(9):1691–1698, doi:10.1016/j.bcp.2004.07.007
On-demand activation of the endocannabinoid system in the control of neuronal excitability and epileptiform seizures.
Neurons intensively exchange information among each other using both inhibitory and excitatory neurotransmitters. However, if the balance of excitation and inhibition is perturbed, the intensity of excitatory transmission may exceed a certain threshold and epileptic seizures can occur. As the occurrence of epilepsy in the human population is about 1%, the search for therapeutic targets to alleviate seizures is warranted. Extracts of Cannabis sativa have a long history in the treatment of various neurological diseases, including epilepsy. However, cannabinoids have been reported to exert both pro- and anti-convulsive activities. The recent progress in understanding the endogenous cannabinoid system has allowed new insights into these opposing effects of cannabinoids. When excessive neuronal activity occurs, endocannabinoids are generated on demand and activate cannabinoid type 1 (CB1) receptors. Using mice lacking CB1 receptors in principal forebrain neurons in a model of epileptiform seizures, it was shown that CB1 receptors expressed on excitatory glutamatergic neurons mediate the anti-convulsive activity of endocannabinoids. Systemic activation of CB1 receptors by exogenous cannabinoids, however, are anti- or pro-convulsive, depending on the seizure model used. The pro-convulsive activity of exogenous cannabinoids might be explained by the notion that CB1 receptors expressed on inhibitory GABAergic neurons are also activated, leading to a decreased release of GABA, and to a concomitant increase in seizure susceptibility. The concept that the endogenous cannabinoid system is activated on demand suggests that a promising strategy to alleviate seizure frequency is the enhancement of endocannabinoid levels by inhibiting the cellular uptake and the degradation of these endogenous compounds.
Cool paper. I suppose chronic THC administration is a likely effective method to activate endocannabinoid system on demand!
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The lesson from administering biologically active opioids and steroids is that they tend to reduce production of the body's natural equivalent, and/or reduce the sensitivity of the receptors.
THC isn't an opioid.... or a steroid, so what exactly are you implying?
Since the body really only works well over a limited range of conditions, the body attempts to maintain "homeostasis (https://en.wikipedia.org/wiki/Homeostasis)" - a constant working environment.
- If you bump up the temperature, the body bumps up sweating to maintain a constant temperature.
- If you bump up glucose intake, the body bumps up insulin to maintain a constant blood glucose level (but then there is a long-term impact on the sensitivity of insulin receptors).
- If you bump up opioid intake, the body reduces its own opioid production and reduces sensitivity of opioid sensors to maintain a constant environment.
- If you bump up cholesterol intake, your body downregulates endogenous cholesterol production.
- Weight lifters often bump up steroid intake, their bodies downregulate endogenous steroid production, with unfortunate impacts on the qualities they were trying to enhance.
I am no expert on the myriad biological pathways interacting with the plethora of biologically active molecules in marijuana, which in turn interact with the huge mix of liver enzyme gene variants spread out around the population. (While there are many experts, I suspect that the complexity of the mix is so great that no-one has a good handle on the interactions at this point in time.)
But if I were to make a very general prediction, I would suggest that the body will attempt to maintain homeostasis. In cases where the ingested compound mimics an internally-produced one, the body is likely to reduce production of the endogenous compound and/or reduce sensitivity of the receptors.
But is not cannabinoid receptor 1 (CB1) responsible for endocannabinoid synthesis?
The Wikipedia section that you quote shows that the cannabinoid receptor is triggered by cannabinoid molecules, and in turn triggers nerve impulses. If the receptor of a molecule also produced more of that molecule, you would have a positive feedback loop that would disable the brain. (Homeostasis requires negative feedback.)
A better reference may be here, which talks about the whole endocannabinoid lifecycle. It comments that some parts of the process are not really understood at this point in time.
https://en.wikipedia.org/wiki/Endocannabinoid_system#Endocannabinoid_synthesis.2C_release.2C_and_degradation
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tkadm30, you will be delighted to hear that marijuana is now legal in my state:
- As prescribed by doctors
- for conditions that have been medically proven to be helped by it
- obtained from licensed sources (effectively the government, at the moment)
- usage will be tracked carefully
"Abnormally low endocannabinoids" is not on the list of demonstrable medical conditions.
See: http://www.sbs.com.au/news/article/2016/07/31/medicinal-cannabis-available-nsw
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But if I were to make a very general prediction, I would suggest that the body will attempt to maintain homeostasis. In cases where the ingested compound mimics an internally-produced one, the body is likely to reduce production of the endogenous compound and/or reduce sensitivity of the receptors.
Cannabis is likely to regulate energy homeostasis: http://www.ncbi.nlm.nih.gov/pubmed/17369778
But is not cannabinoid receptor 1 (CB1) responsible for endocannabinoid synthesis?
The Wikipedia section that you quote shows that the cannabinoid receptor is triggered by cannabinoid molecules, and in turn triggers nerve impulses. If the receptor of a molecule also produced more of that molecule, you would have a positive feedback loop that would disable the brain. (Homeostasis requires negative feedback.)
A better reference may be here, which talks about the whole endocannabinoid lifecycle. It comments that some parts of the process are not really understood at this point in time.
https://en.wikipedia.org/wiki/Endocannabinoid_system#Endocannabinoid_synthesis.2C_release.2C_and_degradation
Thanks for the link.
I'm interested in understanding how endogenous cannabinoid receptor 1 activation contributes to homeostatic energy metabolism. How could endocannabinoid transport regulate homeostatic plasticity? The connection between brain homeostasis and endocannabinoid mobilization is poorly understood.
I don't think endocannabinoids stimulation via exogenous THC administration should create a positive feedback loop because CB1 receptor downregulation will inhibit neurotransmission at GABAergic synapses.
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tkadm30, you will be delighted to hear that marijuana is now legal in my state:
- As prescribed by doctors
- for conditions that have been medically proven to be helped by it
- obtained from licensed sources (effectively the government, at the moment)
- usage will be tracked carefully
"Abnormally low endocannabinoids" is not on the list of demonstrable medical conditions.
See: http://www.sbs.com.au/news/article/2016/07/31/medicinal-cannabis-available-nsw
Thats great news! I also heard that Italy was attempting legalization of cannabis. The global movement for cannabis legalization is starting to heat up!
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Is a adenosine-CB1 heteromer possible? Could allosteric modulation of cannabinoid receptor 1 by adenosine antagonist (caffeine) enhance endocannabinoid synthesis?
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Could stimulation of endocannabinoid levels result in microglial neuroprotection (inhibition of nitric oxide production) through CB1 activation ?
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Does retrograde anandamide signaling facilitate arachidonic acid production?
https://www.ncbi.nlm.nih.gov/pubmed/26213384