The Naked Scientists

The Naked Scientists Forum

Author Topic: How to stimulate endocannabinoid synthesis and uptake?  (Read 1491 times)

Online tkadm30

  • Hero Member
  • *****
  • Posts: 949
  • Thanked: 7 times
    • View Profile
    • IsotopeSoftware
Does THC administration stimulate endocannabinoid synthesis and uptake?

If so, is there any pharmacological alternatives to stimulate endogenous cannabinoid receptors
without THC?





 


 

Offline evan_au

  • Neilep Level Member
  • ******
  • Posts: 4131
  • Thanked: 249 times
    • View Profile
Re: How to stimulate endocannabinoid synthesis and uptake?
« Reply #1 on: 31/07/2016 05:02:37 »
Quote from: tkadm30
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.
 

Online tkadm30

  • Hero Member
  • *****
  • Posts: 949
  • Thanked: 7 times
    • View Profile
    • IsotopeSoftware
Re: How to stimulate endocannabinoid synthesis and uptake?
« Reply #2 on: 31/07/2016 10:57:19 »
Quote from: tkadm30
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?
 

Online tkadm30

  • Hero Member
  • *****
  • Posts: 949
  • Thanked: 7 times
    • View Profile
    • IsotopeSoftware
Re: How to stimulate endocannabinoid synthesis and uptake?
« Reply #3 on: 31/07/2016 10:58:00 »
Quote
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
 

Online exothermic

  • Hero Member
  • *****
  • Posts: 501
  • Thanked: 22 times
    • View Profile
Re: How to stimulate endocannabinoid synthesis and uptake?
« Reply #4 on: 31/07/2016 13:05:31 »
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?
 

Online exothermic

  • Hero Member
  • *****
  • Posts: 501
  • Thanked: 22 times
    • View Profile
Re: How to stimulate endocannabinoid synthesis and uptake?
« Reply #5 on: 31/07/2016 13:12:46 »
Does THC administration stimulate endocannabinoid synthesis and uptake?

Yes.

Quote
Biochemical Pharmacology
1 November 2004, Vol.68(9):16911698, 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.
 
The following users thanked this post: tkadm30

Offline jeffreyH

  • Global Moderator
  • Neilep Level Member
  • *****
  • Posts: 3932
  • Thanked: 55 times
  • The graviton sucks
    • View Profile
Re: How to stimulate endocannabinoid synthesis and uptake?
« Reply #6 on: 31/07/2016 14:40:41 »
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.
 

Offline jeffreyH

  • Global Moderator
  • Neilep Level Member
  • *****
  • Posts: 3932
  • Thanked: 55 times
  • The graviton sucks
    • View Profile
Re: How to stimulate endocannabinoid synthesis and uptake?
« Reply #7 on: 31/07/2016 15:12:34 »
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.
 

Online exothermic

  • Hero Member
  • *****
  • Posts: 501
  • Thanked: 22 times
    • View Profile
Re: How to stimulate endocannabinoid synthesis and uptake?
« Reply #8 on: 31/07/2016 16:49:12 »
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.

~

 

Offline jeffreyH

  • Global Moderator
  • Neilep Level Member
  • *****
  • Posts: 3932
  • Thanked: 55 times
  • The graviton sucks
    • View Profile
Re: How to stimulate endocannabinoid synthesis and uptake?
« Reply #9 on: 31/07/2016 17:04:20 »
What is your mother's maiden name?
« Last Edit: 31/07/2016 17:10:37 by jeffreyH »
 

Offline jeffreyH

  • Global Moderator
  • Neilep Level Member
  • *****
  • Posts: 3932
  • Thanked: 55 times
  • The graviton sucks
    • View Profile
Re: How to stimulate endocannabinoid synthesis and uptake?
« Reply #10 on: 31/07/2016 17:44:31 »
I guess that one isn't included in the enhancement of cognition.
 

Online tkadm30

  • Hero Member
  • *****
  • Posts: 949
  • Thanked: 7 times
    • View Profile
    • IsotopeSoftware
Re: How to stimulate endocannabinoid synthesis and uptake?
« Reply #11 on: 31/07/2016 18:24:19 »
Does THC administration stimulate endocannabinoid synthesis and uptake?

Yes.

Quote
Biochemical Pharmacology
1 November 2004, Vol.68(9):16911698, 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!
 

Offline evan_au

  • Neilep Level Member
  • ******
  • Posts: 4131
  • Thanked: 249 times
    • View Profile
Re: How to stimulate endocannabinoid synthesis and uptake?
« Reply #12 on: 31/07/2016 23:56:40 »
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" - 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.

Quote from: tkadm30
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
 

Offline evan_au

  • Neilep Level Member
  • ******
  • Posts: 4131
  • Thanked: 249 times
    • View Profile
Re: How to stimulate endocannabinoid synthesis and uptake?
« Reply #13 on: 01/08/2016 11:02:05 »
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
 

Online tkadm30

  • Hero Member
  • *****
  • Posts: 949
  • Thanked: 7 times
    • View Profile
    • IsotopeSoftware
Re: How to stimulate endocannabinoid synthesis and uptake?
« Reply #14 on: 01/08/2016 11:11:12 »
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

Quote from: evan_au
Quote from: tkadm30
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.
 

Online tkadm30

  • Hero Member
  • *****
  • Posts: 949
  • Thanked: 7 times
    • View Profile
    • IsotopeSoftware
Re: How to stimulate endocannabinoid synthesis and uptake?
« Reply #15 on: 01/08/2016 11:16:13 »
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!
 

Online tkadm30

  • Hero Member
  • *****
  • Posts: 949
  • Thanked: 7 times
    • View Profile
    • IsotopeSoftware
Re: How to stimulate endocannabinoid synthesis and uptake?
« Reply #16 on: 01/08/2016 20:07:43 »
Is a adenosine-CB1 heteromer possible? Could allosteric modulation of cannabinoid receptor 1 by adenosine antagonist (caffeine) enhance endocannabinoid synthesis?
 

Online tkadm30

  • Hero Member
  • *****
  • Posts: 949
  • Thanked: 7 times
    • View Profile
    • IsotopeSoftware
Re: How to stimulate endocannabinoid synthesis and uptake?
« Reply #17 on: 17/10/2016 10:51:00 »
Could stimulation of endocannabinoid levels result in microglial neuroprotection (inhibition of nitric oxide production) through CB1 activation ?

 

Online tkadm30

  • Hero Member
  • *****
  • Posts: 949
  • Thanked: 7 times
    • View Profile
    • IsotopeSoftware
Re: How to stimulate endocannabinoid synthesis and uptake?
« Reply #18 on: 05/11/2016 12:10:55 »
Does retrograde anandamide signaling facilitate arachidonic acid production?

https://www.ncbi.nlm.nih.gov/pubmed/26213384
 

The Naked Scientists Forum

Re: How to stimulate endocannabinoid synthesis and uptake?
« Reply #18 on: 05/11/2016 12:10:55 »

 

SMF 2.0.10 | SMF © 2015, Simple Machines
SMFAds for Free Forums
 
Login
Login with username, password and session length