Sponsored by

PuffItUp Dynavap VGoodiez 420EDC Dispensr
  • Welcome to VaporAsylum! Please take a moment to read our RULES and introduce yourself here.
  • Need help navigating the forum? Find out how to use our features here.
  • Did you know we have lots of smilies for you to use?

Meds Why Coffee Could Be the Opposite of Cannabis

Baron23

Well-Known Member
Why Coffee Could Be the Opposite of Cannabis

What does coffee have to do with cannabis? According to a new study, your morning joe causes a drop in the levels of certain substances that are linked to the body's system for responding to marijuana.

The levels of these substances — metabolites found in what's known as the endocannabinoid system — decrease in people who drink between four and eight cups of coffee a day, according to the study, published today (March 15) in the Journal of Internal Medicine. Endocannabinoids are molecules that bind to cannabinoid receptors, which are found all over the nervous system, as well as in immune and endocrine tissue. The body makes its own endocannabinoids, but it also responds to foreign cannabinoids, like the ones found in the leaves of plants of the Cannabis genus.

Coffee suppresses the endocannabinoid chemicals that smoking marijuana boosts, said Marilyn Cornelis, an assistant professor of preventative medicine at Northwestern University's Feinberg School of Medicine, who led the new research. [25 Odd Facts About Marijuana]

That would suggest that coffee might generate the opposite effects as cannabis on the endocannabinoid system, Cornelis told Live Science.

Your blood on coffee
The research didn't look at the sensations or behaviors that coffee produces compared to cannabis, only at the rise and fall of chemicals in the blood after coffee consumption. Endocannabinoids were just one set of the chemicals — or metabolites — that changed, the researchers found. All told, coffee altered 115 different metabolites in the blood. Thirty-four of those metabolites don't even have names or known roles in the body. The other 82 known metabolites play roles in 33 different biological processes.

Cornelis and her team focused on five of these specific biological processes where numerous metabolites seemed to cluster. Two of the processes were expected: One was xanthine metabolism — a set of processes that includes caffeine metabolism, which made sense, because the body naturally has to metabolize the caffeine in coffee once it is consumed. The other pathway, benzoate metabolism, in involved in breaking down other compounds in coffee called polyphenols. The compounds are broken down by microbes that live in the gut, Cornelis said. The gut microbiome is under increased scrutiny for its role in health, so the finding is intriguing, she said.

But the real surprises were three other metabolic processes never before linked with coffee. Endocannabinoids were clustered in one of those processes.

"What we're seeing here is that the systems that are impacted by coffee and cannabis overlap," Cornelis said. That could mean that drinking coffee with marijuana in your system could create interacting effects, she said, though the nature of those interactions isn't yet clear. Typically, she said, the same endocannabinoids that declined with coffee also decrease when the body is under stress. It's possible that the amount of coffee that participants were drinking (four to eight cups a day) caused stress, which led to a drop of endocannabinoid levels as some kind of protective measure.

Cornelis and her team also found that coffee consumption increased the concentration of steroid metabolites in the blood, possibly because coffee contains plant steroids called phytosterols. In particular, the metabolites that increased are linked to steroid excretion, Cornelis said, so it's possible that coffee could boost steroid breakdown in the body. (Greater steroid breakdown would lead to greater steroid excretion.)

What this finding means for human health remains a mystery. Some steroid processes have links to certain cancers, Cornelis said, and the link between coffee itself and cancer is fuzzy, so the steroid finding could provide a new place to look to understand whether coffee consumption affects the likelihood of a person developing cancer.

The final grouping of metabolites changed by coffee consumption consisted of fatty acid acylcholines, which may be linked with the endocannabinoid pathway, Cornelis said. But the changes there are the most mysterious of all.

"That's a novel set of metabolites that we don't really know how to explain," she said.

Coffee and health
That the study raised more questions than answers is no surprise: Cornelis went into the research hunting for new links between coffee and health. Plenty of research has associated coffee drinking with health effects, she said — so much so that Coffee Is Good For You/Coffee Is Bad For You headlines are almost a cliche. [10 Things You Need to Know About Coffee]

But those are just statistical associations, Cornelis said. "The goal of my research is to understand the causal reasons that link coffee to those outcomes."

The current study is based on a years-old clinical trial conducted in Finland, where 47 coffee drinkers were asked to abstain from the brew for one month, then drink four cups a day for a month, then escalate to eight cups a day for the final month of the study. All participants drank the same medium-roast arabica blend, which is also the most popular type of coffee in the United States, Cornelis said. Cornelis and her team used the blood of these participants to test 733 metabolites.

The same people were also tested for changes in their levels of lipids and proteins, which is what Cornelis is studying next. She also hopes to use other data from large, population-based studies that included data on coffee consumption to see if the same metabolites change in broader populations.

"It would be interesting to see if there were some genetic differences in the response to coffee as well," she said.
 

ataxian

In a BLACK HOLE!
Why Coffee Could Be the Opposite of Cannabis

What does coffee have to do with cannabis? According to a new study, your morning joe causes a drop in the levels of certain substances that are linked to the body's system for responding to marijuana.

The levels of these substances — metabolites found in what's known as the endocannabinoid system — decrease in people who drink between four and eight cups of coffee a day, according to the study, published today (March 15) in the Journal of Internal Medicine. Endocannabinoids are molecules that bind to cannabinoid receptors, which are found all over the nervous system, as well as in immune and endocrine tissue. The body makes its own endocannabinoids, but it also responds to foreign cannabinoids, like the ones found in the leaves of plants of the Cannabis genus.

Coffee suppresses the endocannabinoid chemicals that smoking marijuana boosts, said Marilyn Cornelis, an assistant professor of preventative medicine at Northwestern University's Feinberg School of Medicine, who led the new research. [25 Odd Facts About Marijuana]

That would suggest that coffee might generate the opposite effects as cannabis on the endocannabinoid system, Cornelis told Live Science.

Your blood on coffee
The research didn't look at the sensations or behaviors that coffee produces compared to cannabis, only at the rise and fall of chemicals in the blood after coffee consumption. Endocannabinoids were just one set of the chemicals — or metabolites — that changed, the researchers found. All told, coffee altered 115 different metabolites in the blood. Thirty-four of those metabolites don't even have names or known roles in the body. The other 82 known metabolites play roles in 33 different biological processes.

Cornelis and her team focused on five of these specific biological processes where numerous metabolites seemed to cluster. Two of the processes were expected: One was xanthine metabolism — a set of processes that includes caffeine metabolism, which made sense, because the body naturally has to metabolize the caffeine in coffee once it is consumed. The other pathway, benzoate metabolism, in involved in breaking down other compounds in coffee called polyphenols. The compounds are broken down by microbes that live in the gut, Cornelis said. The gut microbiome is under increased scrutiny for its role in health, so the finding is intriguing, she said.

But the real surprises were three other metabolic processes never before linked with coffee. Endocannabinoids were clustered in one of those processes.

"What we're seeing here is that the systems that are impacted by coffee and cannabis overlap," Cornelis said. That could mean that drinking coffee with marijuana in your system could create interacting effects, she said, though the nature of those interactions isn't yet clear. Typically, she said, the same endocannabinoids that declined with coffee also decrease when the body is under stress. It's possible that the amount of coffee that participants were drinking (four to eight cups a day) caused stress, which led to a drop of endocannabinoid levels as some kind of protective measure.

Cornelis and her team also found that coffee consumption increased the concentration of steroid metabolites in the blood, possibly because coffee contains plant steroids called phytosterols. In particular, the metabolites that increased are linked to steroid excretion, Cornelis said, so it's possible that coffee could boost steroid breakdown in the body. (Greater steroid breakdown would lead to greater steroid excretion.)

What this finding means for human health remains a mystery. Some steroid processes have links to certain cancers, Cornelis said, and the link between coffee itself and cancer is fuzzy, so the steroid finding could provide a new place to look to understand whether coffee consumption affects the likelihood of a person developing cancer.

The final grouping of metabolites changed by coffee consumption consisted of fatty acid acylcholines, which may be linked with the endocannabinoid pathway, Cornelis said. But the changes there are the most mysterious of all.

"That's a novel set of metabolites that we don't really know how to explain," she said.

Coffee and health
That the study raised more questions than answers is no surprise: Cornelis went into the research hunting for new links between coffee and health. Plenty of research has associated coffee drinking with health effects, she said — so much so that Coffee Is Good For You/Coffee Is Bad For You headlines are almost a cliche. [10 Things You Need to Know About Coffee]

But those are just statistical associations, Cornelis said. "The goal of my research is to understand the causal reasons that link coffee to those outcomes."

The current study is based on a years-old clinical trial conducted in Finland, where 47 coffee drinkers were asked to abstain from the brew for one month, then drink four cups a day for a month, then escalate to eight cups a day for the final month of the study. All participants drank the same medium-roast arabica blend, which is also the most popular type of coffee in the United States, Cornelis said. Cornelis and her team used the blood of these participants to test 733 metabolites.

The same people were also tested for changes in their levels of lipids and proteins, which is what Cornelis is studying next. She also hopes to use other data from large, population-based studies that included data on coffee consumption to see if the same metabolites change in broader populations.

"It would be interesting to see if there were some genetic differences in the response to coffee as well," she said.
COFFEE (EPRESSO) Don't Ban it!
CANNABIS Don't Ban it!
NbbMxKd.jpg

CIVILIZED 420
 

momofthegoons

Vapor Accessory Addict
Staff member
So @Baron23 what's your thoughts on this? I'm not sure what I think.

Of course... I don't function well without my two cups of coffee in the morning. Anyone who's gotten a pm from me before I've had my coffee knows.... :lol:). So I may not be the best person to ask.
 

Baron23

Well-Known Member
So @Baron23 what's your thoughts on this? I'm not sure what I think.

Of course... I don't function well without my two cups of coffee in the morning. Anyone who's gotten a pm from me before I've had my coffee knows.... :lol:). So I may not be the best person to ask.


decrease in people who drink between four and eight cups of coffee a day

Well, I have cut my coffee consumption down to one to one and half large mugs in the morning and that's it.

Frankly, I don't care what my Endocannabinoid system thinks of it....without that cup of coffee I don't even begin to breath! LOL

So suck it up, brain receptors...this is just how its got to be. LOL
 

ataxian

In a BLACK HOLE!
Well, I have cut my coffee consumption down to one to one and half large mugs in the morning and that's it.

Frankly, I don't care what my Endocannabinoid system thinks of it....without that cup of coffee I don't even begin to breath! LOL

So suck it up, brain receptors...this is just how its got to be. LOL
I drink one double espresso (FRENCH STYLE) I want more however my wife cut's me off.
SHE say's "Your too HYPER"! One is all I get?

CANNABIS most of the waking hours?

That's my story!

420 infused with wine is a different subject!
 

momofthegoons

Vapor Accessory Addict
Staff member
More on how coffee and cannabis may not be a good mix...
I'm with @Baron23 though; I need my 2 cups of strong coffee in the morning or I can't function. But that's all the caffeine I consume in a day.

COFFEE AND CANNABIS
Is it a good idea to mix CBD or THC with caffeine?

Highlights:
  • Caffeine and cannabinoids have many opposing effects on the body and mind.
  • Caffeine amplifies THC’s ability to temporarily impair memory due to interactions with adenosine receptors.
  • Low doses of CBD are unlikely to be affected by caffeine. But caffeine may counter the sedating effects of high doses of CBD.
  • Some of CBD’s anti-inflammatory effects could be prevented by caffeine.
  • A number of plant cannabinoids will impede and slow the breakdown of caffeine.


Glossary of abbreviations:

  • A1 (adenosine receptor 1): Adenosine-sensitive receptor that plays a role in brain signaling and cardiovascular function. It is inhibited by caffeine.
  • A2A (adenosine receptor 2A): Anti-inflammatory adenosine-sensitive receptor that is present in the brain and heart. It is also inhibited by caffeine.
  • cAMP (cyclic adenosine monophosphate): A major intracellular messenger that can be generated by activation of cannabinoid or adenosine receptors.
  • CB1 (cannabinoid receptor 1): One of the two major cannabinoid receptors. Responsible for THC’s high.
  • CBD (cannabidiol): A non-intoxicating plant cannabinoid.
  • CBN (cannabinol): A plant cannabinoid produced when THC is left in heat or sunlight.
  • LTD (long term depression): A type of brain plasticity where individual neurons become less excitable, neuronal activity is reduced, and connections between cells are weakened.
  • LTP (long term potentiation): A type of brain plasticity where individual neurons become more excitable and connections between cells are strengthened. It is involved in learning and memory.
  • PDE (phosphodiesterase): A cellular enzyme that breaks down cAMP and related chemicals.
  • THC (tetrahydrocannabinol): The cannabinoid in cannabis most responsible for causing a high.
xcannabis_and_coffee.jpg,qitok=qmgQBzXh.pagespeed.ic.Jifrlvwgum.jpg

Is it a good idea to mix CBD or THC with caffeine?
Coffee and cannabis are two of the most widely used psychoactive substances in the world. Whereas cannabis is often consumed to relax the body, enhance perception, and stimulate creativity, coffee – like tea and other caffeinated beverages – is typically used to energize and help people focus, particularly in the face of exhaustion.

Does it make sense to consume cannabis and coffee together? How do they interact? Is it fitting that decriminalized THC-rich cannabis was first sold over-the-counter in Amsterdam’s coffee shops?

More recently, several unregulated cannabis start-ups have begun producing and selling coffee infused with doses of hemp-derived CBD. Are caffeine and cannabidiol truly a good combo, or is this just a clever marketing gimmick?

Opposite effects
Caffeine is typically thought of as a mild cognitive enhancer. It increases one’s ability to focus and can improve short term memory. Physiologically, caffeine promotes fat metabolism and wards off sleepiness. These effects are mostly opposite those of THC, which can also help one focus, but briefly impairs short term memory while decreasing fat metabolism. [1]

Caffeine is a stimulant that activates the sympathetic nervous system, which is intrinsic to the basic human stress-response. But THC mitigates many of the effects of stress. Paradoxically, THC can even restore memory in animals impaired by chronic stress. When coffee and cannabis are combined, which effects win out?

Since plant-cannabinoids like THC and CBD weakly inhibit the metabolism of caffeine by blocking an enzyme called CYP1A2, one might expect that caffeine would overpower the cannabinoids. [2]



xmemory_impairment.jpg,qitok=4cR3jIT4.pagespeed.ic.B1NDWwP41K.jpg

As it turns out, their interaction is not so straightforward. Caffeine actually amplifies memory impairment caused by THC. And this effect may be specific to short-term memory. To understand how this happens, it’s necessary to look at the neurological properties of these special compounds.

Low & high doses of caffeine
Caffeine has two major biochemical effects. At low doses it blocks adenosine receptors (A1, A2A, and A3). These receptors are typically associated with sleepiness. Adenosine regulates the sleep-wake cycle and regulates the dilation and constriction of blood vessels. The stimulating effects of coffee and tea are due to the inhibition of adenosine receptors. And the headaches that some people experience during caffeine withdrawal are likely due to constriction of blood vessels in the brain.

At higher doses, caffeine inhibits a type of enzyme called a phosphodiesterase (PDE). PDEs break down important chemical messengers that are generated by both cannabinoid and adenosine receptors. These messengers are called cyclic AMP (cAMP) and the related cGMP. They are some of the most common signaling molecules in cells. [3]

PDE enzymes are a target of asthma medications, as well as Viagra.

Adenosine: CB1 gatekeeper


xadenosine.jpg,qitok=EPK4rmkN.pagespeed.ic.nMfT4jdfUp.jpg

CB1 cannabinoid receptors and A1 adenosine receptors both populate the hippocampus – a region of the brain responsible for many aspects of memory. Short-term memory, in particular, is processed by brief neurological changes in the hippocampus. When hippocampal A1 is highly activated, the efficacy of cannabinoids at CB1 is reduced. THC, endocannabinoids or an experimental synthetic cannabinoid will still be able to activate CB1, but even high doses will produce a smaller effect.

In a 2011 study led by Portuguese scientists at the University of Lisbon, THC’s effect was one third as strong when given along with an A1 adenosine receptor agonist. (An agonist activates a receptor; an antagonist blocks the receptor.) Conversely, blocking the A1 receptor would increase the effect of cannabinoids, but only in situations where A1 is already active. [4] The precise mechanism by which A1reduces CB1’s efficacy is still unclear.

This research suggests that elevating adenosine levels might protect people from THC-induced memory impairment without diminishing THC’s important effects outside of the hippocampus, which include neuroprotection, reduction of nausea, and painkilling, as well as psychoactivity. Adenosine levels are highest before sleep. So nighttime use of cannabis may have a lesser effect on memory than daytime use, though this has not been tested experimentally.

In cases where cannabis is used to ease trauma, caffeine drinkers may end up benefiting by combining the herb or its components with a cup of Joe. But this might not be the case for a stressed employee who drinks coffee to get through the day. A few preliminary studies have shown that drinking coffee occasionally or frequently had the same effect: Both amplified THC’s ability to temporarily weaken memory.


The neurology of memory


xexpression-mechanisms-of-long-term-depression-and-presynaptic-long-term-potentiation.png,qitok=GOt5mvSc.pagespeed.ic.c9EAnve_Ct.jpg

Expression mechanisms of LTD and presynaptic LTP.
So how does THC actually affect short-term memory?

Memory is not encoded in the firing of a single neuron – it develops through changes in the brain’s network. If certain connections between neurons are highly utilized, it would make sense for the brain to strengthen those pathways. On the other hand, if two neurons rarely communicate, it would be better not to expend much energy maintaining the connection. The dynamic strengthening and elimination of neural connections is a key aspect of brain plasticity.

Endocannabinoids play a significant role in synaptic plasticity (and overall neuroplasticity) by regulating what scientists refer to as “long-term potentiation” (LTP) and “long-term depression” (LTD). Both of these processes have a direct bearing on memory and many other brain functions.

LTP involves potentiating or strengthening neural connections between cells; this can occur by increasing the amount of neurotransmitters released by the presynaptic (signal-sending) neuron or by heightening the sensitivity of the postsynaptic (signal-receiving) neuron. LTD entails the opposite process, which ultimately reduces the effect of neuronal activity. LTD in the hippocampus facilitates the clearance of old memories.

Endogenous cannabinoids and plant cannabinoids inhibit neurotransmitter release by activating the CB1receptor. This can result in bidirectional physiological effects depending on which neurotransmitters are inhibited. CB1 exists on both excitatory (glutamatergic) and inhibitory (GABAergic) neurons. When CB1impedes the release of GABA, an inhibitory neurotransmitter, CB1 increases (“disinhibits”) brain activity. And by slowing glutamatergic neurons, cannabinoids (via CB1) generally promote LTD and the removal of old memories in the hippocampus. [5]

Fine-tuning the brain
Adenosine is constantly released in small concentrations onto the same part of the hippocampus where cannabinoid, adenosine, and glutamate receptors reside. Adenosine, by activating the A1 receptor, reduces the efficacy of THC and other cannabinoids at CB1. And this partially suppresses cannabinoid-mediated LTD, thereby enhancing short-term memory.

But caffeine blocks A1 receptors. This amplifies the impact of cannabinoid activity and, in turn, will lead to greater LTD and temporary impairments in working memory. [6]

CB1 and A1 receptors also exist on GABAergic neurons in the hippocampus. A1 plays a similar gatekeeping role for CB1 in these neurons (it impedes CB1’s suppression of the inhibitory neurotransmitter GABA). GABAergic neurons act as the major brake slowing glutamate release in the hippocampus. [7]

By engaging the CB1 receptor, cannabinoids can promote either LTD or LTP under different circumstances. LTD appears to be more common. Adenosine acting at A1 receptors will enhance memory by reducing LTD. These complex interactions and feedback loops provide neurons with subtle means to fine-tune the brain.

CBD and adenosine


xadenosine_and_caffeine.jpg,qitok=z_cnbmct.pagespeed.ic.6k0JPzWU_U.jpg

Cannabidiol does not directly activate CB1, but exerts effects through many other pathways. For example, high doses of CBD elevate adenosine levels in the brain by preventing the reuptake of adenosine. This may account for CBD’s ability to ameliorate the short-term memory impairments attributed to THCin some studies. It could be one of many mechanisms that contribute to the “ensemble effect,” whereby the variety of compounds in cannabis can mitigate each other’s side effects and promote each other’s efficacy.

Adenosine is not just a neurotransmitter; it is also known to have intrinsic anti-inflammatory effects. Its reuptake is the main way the body terminates adenosine signaling. Cannabidiol is protective in some models of heart attack, multiple sclerosis, lung injury, and retinal problems because CBD indirectly activates (via adenosine reuptake inhibition) A2A and A1 receptors.

The sedative side effect of high doses of CBD might also be related to amplified adenosine. In clinical trials of a sublingual CBD isolate called Epidiolex, sedation is one of the most common side effects. Although the molecular cause of this is not known with certainty, a high dose of CBD may augment adenosine signaling and contribute to tiredness.

When mixed with caffeine, CBD’s effects on adenosine would probably be dwarfed by caffeine’s antagonistic activity at adenosine receptors. The extent to which this might diminish CBD’s medicinal properties is unknown. Given cannabidiol’s many modes of action, it is unlikely that this would be seriously problematic. But as of now, there aren’t clear advantages to combining or marketing CBD and caffeine together.

Adrian Devitt-Lee is a Project CBD contributing writer.

Footnotes

1. The role of THC and CB1 in fat metabolism is not fully understood. At a cellular level, peripheral CB1receptor activation decreases the metabolism of fat. And cannabinoids, of course, are known to cause the munchies. But cannabis use in the general population is associated with lower rates of metabolic syndrome (type 2 diabetes, obesity, and related complications).
2. Caffeine is broken down to other active chemicals, so altering the metabolic pathway may not simply increase the stimulant effect. As well, cannabinol (CBN), which is formed when THC is broken down by exposure to sunlight or heat, was 30-100 times more potent in blocking metabolism than either CBD or THC.
3. Adenosine, in addition to playing a role in neurotransmission, forms the chemical backbone of cAMP and the related molecule ATP (adenosine triphosphate). ATP is the cell’s chemical battery.
4. Tonic activity occurs when adenosine is constantly released in small concentrations, meaning that A1 is always activated to some degree. Other receptors are constitutively active, meaning they sometimes “turn on” even in the absence of an agonist. In the absence of receptor activity, an inhibitor has no effect. But when a receptor is tonically or constitutively active, antagonists can lower receptor activity to a level below normal. Such drugs are called “inverse agonists,” to distinguish them from “neutral antagonists” that decrease receptor activity to normal, but not lower than normal. Interestingly, this is one reason why animal studies of cannabinoids don’t always hold up across different species. Even mice and rats have different tonic concentrations of adenosine in the brain.
5. The endocannabinoid system promotes homeostasis and is rarely one-directional. Although it generally increases LTD, which weakens synapses to allow other synapses room to grow stronger, it can also do the reverse. In chronically stressed animals where LTP was reduced, CB1 activation restored plasticity by promoting LTP.
6. Although CB1 receptors exist on presynaptic neurons, A1 receptors are expressed on both the pre- and postsynaptic neurons. On the presynaptic side, A1 reduces the efficacy of CB1. But on the postsynaptic side, A1 is inhibitory and opposes the effect of glutamate. By inhibiting postsynaptic A1, the neuron may become more excitable, cascading to endocannabinoid release and even greater activation of presynaptic CB1receptors. Hence, adenosine may be dually inhibiting CB1 activity in this specific set of hippocampal neurons.
7. Beyond the hippocampus, cannabinoids affect memory in a brain region called the amygdala. The amygdala is involved in emotional memories, particularly fear. Research has suggested that without CB1receptors in the amygdala, animals are unable to forget fearful memories. The second adenosine receptor subtype, A2A, is known to be involved in memory as well. In the amygdala, decreased A2A levels are associated with greater fear extinction, suggesting that A2A may play a role in inhibiting CB1 signaling. These interactions, however, have not been studied as of yet. Neither are there studies on how caffeine and cannabinoids interact in their regulation of fat metabolism or the physiological stress response.



Sources

Abush H, Akirav I. Cannabinoids ameliorate impairments induced by chronic stress to synaptic plasticity and short-term memory. Neuropsychopharmacology. 2013;38(8):1521-1534.

Carrier EJ, Auchampach JA, Hillard CJ. Inhibition of an equilibrative nucleoside transporter by cannabidiol: A mechanism of cannabinoid immunosuppression. Proc Natl Acad Sci. 2006;103(20):7895-7900.

Chevaleyre V, Castillo PE. Heterosynaptic LTD of hippocampal GABAergic synapses: A novel role of endocannabinoids in regulating excitability. Neuron. 2003;38(3):461-472.

Durst R, Danenberg H, Gallily R, et al. Cannabidiol, a nonpsychoactive Cannabis constituent, protects against myocardial ischemic reperfusion injury. Am J Physiol Circ Physiol. 2007;293(6):H3602-H3607.

Gonca E, Darici F. The Effect of Cannabidiol on ischemia/reperfusion-induced ventricular arrhythmias: The role of adenosine A1 receptors. J Cardiovasc Pharmacol Ther. 2015;20(1):76-83.

Hampson RE, Miller F, Palchik G, Deadwyler SA. Cannabinoid receptor activation modifies NMDA receptor mediated release of intracellular calcium: Implications for endocannabinoid control of hippocampal neural plasticity. Neuropharmacology. 2011;60(6):944-952.

Hoffman AF, Laaris N, Kawamura M, Masino SA, Lupica CR. Control of Cannabinoid CB1 Receptor Function on Glutamate Axon Terminals by Endogenous Adenosine Acting at A1 Receptors. J Neurosci. 2010;30(2):545-555.

Liou GI, Auchampach JA, Hillard CJ, et al. Mediation of cannabidiol anti-inflammation in the retina by equilibrative nucleoside transporter and A2A adenosine receptor. Investig Ophthalmol Vis Sci. 2008;49(12):5526-5531.

Mijangos-Moreno S, Poot-Aké A, Arankowsky-Sandoval G, Murillo-Rodríguez E.
Intrahypothalamic injection of cannabidiol increases the extracellular levels of adenosine in nucleus accumbens in rats. Neurosci Res. 2014;84:60-63.

Panlilio L V., Ferré S, Yasar S, Thorndike EB, Schindler CW, Goldberg SR. Combined effects of THC and caffeine on working memory in rats. Br J Pharmacol. 2012;165(8):2529-2538.

Peterfi Z, Urban GM, Papp OI, et al. Endocannabinoid-Mediated Long-Term Depression of Afferent Excitatory Synapses in Hippocampal Pyramidal Cells and GABAergic Interneurons. J Neurosci. 2012;32(41):14448-14463.

Shoshan N, Segev A, Abush H, Mizrachi Zer-Aviv T, Akirav I. Cannabinoids prevent the differential long-term effects of exposure to severe stress on hippocampal- and amygdala-dependent memory and plasticity. Hippocampus. 2017;27(10):1093-1109.

Sousa VC, Assaife-Lopes N, Ribeiro JA, Pratt JA, Brett RR, Sebastião AM. Regulation of hippocampal cannabinoid CB1 receptor actions by adenosine A1 receptors and chronic caffeine administration: Implications for the effects of Δ9-tetrahydrocannabinol on spatial memory. Neuropsychopharmacology. 2011;36(2):472-487.

Yamaori S, Kushihara M, Yamamoto I, Watanabe K. Characterization of major phytocannabinoids, cannabidiol and cannabinol, as isoform-selective and potent inhibitors of human CYP1 enzymes. Biochem Pharmacol. 2010;79(11):1691-1698.


 

ataxian

In a BLACK HOLE!
More on how coffee and cannabis may not be a good mix...
I'm with @Baron23 though; I need my 2 cups of strong coffee in the morning or I can't function. But that's all the caffeine I consume in a day.

COFFEE AND CANNABIS

Is it a good idea to mix CBD or THC with caffeine?

Highlights:



    • Caffeine and cannabinoids have many opposing effects on the body and mind.
    • Caffeine amplifies THC’s ability to temporarily impair memory due to interactions with adenosine receptors.
    • Low doses of CBD are unlikely to be affected by caffeine. But caffeine may counter the sedating effects of high doses of CBD.
    • Some of CBD’s anti-inflammatory effects could be prevented by caffeine.
    • A number of plant cannabinoids will impede and slow the breakdown of caffeine.

Glossary of abbreviations:




    • A1 (adenosine receptor 1): Adenosine-sensitive receptor that plays a role in brain signaling and cardiovascular function. It is inhibited by caffeine.
    • A2A (adenosine receptor 2A): Anti-inflammatory adenosine-sensitive receptor that is present in the brain and heart. It is also inhibited by caffeine.
    • cAMP (cyclic adenosine monophosphate): A major intracellular messenger that can be generated by activation of cannabinoid or adenosine receptors.
    • CB1 (cannabinoid receptor 1): One of the two major cannabinoid receptors. Responsible for THC’s high.
    • CBD (cannabidiol): A non-intoxicating plant cannabinoid.
    • CBN (cannabinol): A plant cannabinoid produced when THC is left in heat or sunlight.
    • LTD (long term depression): A type of brain plasticity where individual neurons become less excitable, neuronal activity is reduced, and connections between cells are weakened.
    • LTP (long term potentiation): A type of brain plasticity where individual neurons become more excitable and connections between cells are strengthened. It is involved in learning and memory.
    • PDE (phosphodiesterase): A cellular enzyme that breaks down cAMP and related chemicals.
    • THC (tetrahydrocannabinol): The cannabinoid in cannabis most responsible for causing a high.

Is it a good idea to mix CBD or THC with caffeine?
Coffee and cannabis are two of the most widely used psychoactive substances in the world. Whereas cannabis is often consumed to relax the body, enhance perception, and stimulate creativity, coffee – like tea and other caffeinated beverages – is typically used to energize and help people focus, particularly in the face of exhaustion.

Does it make sense to consume cannabis and coffee together? How do they interact? Is it fitting that decriminalized THC-rich cannabis was first sold over-the-counter in Amsterdam’s coffee shops?

More recently, several unregulated cannabis start-ups have begun producing and selling coffee infused with doses of hemp-derived CBD. Are caffeine and cannabidiol truly a good combo, or is this just a clever marketing gimmick?

Opposite effects

Caffeine is typically thought of as a mild cognitive enhancer. It increases one’s ability to focus and can improve short term memory. Physiologically, caffeine promotes fat metabolism and wards off sleepiness. These effects are mostly opposite those of THC, which can also help one focus, but briefly impairs short term memory while decreasing fat metabolism. [1]

Caffeine is a stimulant that activates the sympathetic nervous system, which is intrinsic to the basic human stress-response. But THC mitigates many of the effects of stress. Paradoxically, THC can even restore memory in animals impaired by chronic stress. When coffee and cannabis are combined, which effects win out?

Since plant-cannabinoids like THC and CBD weakly inhibit the metabolism of caffeine by blocking an enzyme called CYP1A2, one might expect that caffeine would overpower the cannabinoids. [2]



As it turns out, their interaction is not so straightforward. Caffeine actually amplifies memory impairment caused by THC. And this effect may be specific to short-term memory. To understand how this happens, it’s necessary to look at the neurological properties of these special compounds.

Low & high doses of caffeine

Caffeine has two major biochemical effects. At low doses it blocks adenosine receptors (A1, A2A, and A3). These receptors are typically associated with sleepiness. Adenosine regulates the sleep-wake cycle and regulates the dilation and constriction of blood vessels. The stimulating effects of coffee and tea are due to the inhibition of adenosine receptors. And the headaches that some people experience during caffeine withdrawal are likely due to constriction of blood vessels in the brain.

At higher doses, caffeine inhibits a type of enzyme called a phosphodiesterase (PDE). PDEs break down important chemical messengers that are generated by both cannabinoid and adenosine receptors. These messengers are called cyclic AMP (cAMP) and the related cGMP. They are some of the most common signaling molecules in cells. [3]

PDE enzymes are a target of asthma medications, as well as Viagra.

Adenosine: CB1 gatekeeper




CB1 cannabinoid receptors and A1 adenosine receptors both populate the hippocampus – a region of the brain responsible for many aspects of memory. Short-term memory, in particular, is processed by brief neurological changes in the hippocampus. When hippocampal A1 is highly activated, the efficacy of cannabinoids at CB1 is reduced. THC, endocannabinoids or an experimental synthetic cannabinoid will still be able to activate CB1, but even high doses will produce a smaller effect.

In a 2011 study led by Portuguese scientists at the University of Lisbon, THC’s effect was one third as strong when given along with an A1 adenosine receptor agonist. (An agonist activates a receptor; an antagonist blocks the receptor.) Conversely, blocking the A1 receptor would increase the effect of cannabinoids, but only in situations where A1 is already active. [4] The precise mechanism by which A1reduces CB1’s efficacy is still unclear.

This research suggests that elevating adenosine levels might protect people from THC-induced memory impairment without diminishing THC’s important effects outside of the hippocampus, which include neuroprotection, reduction of nausea, and painkilling, as well as psychoactivity. Adenosine levels are highest before sleep. So nighttime use of cannabis may have a lesser effect on memory than daytime use, though this has not been tested experimentally.

In cases where cannabis is used to ease trauma, caffeine drinkers may end up benefiting by combining the herb or its components with a cup of Joe. But this might not be the case for a stressed employee who drinks coffee to get through the day. A few preliminary studies have shown that drinking coffee occasionally or frequently had the same effect: Both amplified THC’s ability to temporarily weaken memory.


The neurology of memory




Expression mechanisms of LTD and presynaptic LTP.
So how does THC actually affect short-term memory?

Memory is not encoded in the firing of a single neuron – it develops through changes in the brain’s network. If certain connections between neurons are highly utilized, it would make sense for the brain to strengthen those pathways. On the other hand, if two neurons rarely communicate, it would be better not to expend much energy maintaining the connection. The dynamic strengthening and elimination of neural connections is a key aspect of brain plasticity.

Endocannabinoids play a significant role in synaptic plasticity (and overall neuroplasticity) by regulating what scientists refer to as “long-term potentiation” (LTP) and “long-term depression” (LTD). Both of these processes have a direct bearing on memory and many other brain functions.

LTP involves potentiating or strengthening neural connections between cells; this can occur by increasing the amount of neurotransmitters released by the presynaptic (signal-sending) neuron or by heightening the sensitivity of the postsynaptic (signal-receiving) neuron. LTD entails the opposite process, which ultimately reduces the effect of neuronal activity. LTD in the hippocampus facilitates the clearance of old memories.

Endogenous cannabinoids and plant cannabinoids inhibit neurotransmitter release by activating the CB1receptor. This can result in bidirectional physiological effects depending on which neurotransmitters are inhibited. CB1 exists on both excitatory (glutamatergic) and inhibitory (GABAergic) neurons. When CB1impedes the release of GABA, an inhibitory neurotransmitter, CB1 increases (“disinhibits”) brain activity. And by slowing glutamatergic neurons, cannabinoids (via CB1) generally promote LTD and the removal of old memories in the hippocampus. [5]

Fine-tuning the brain

Adenosine is constantly released in small concentrations onto the same part of the hippocampus where cannabinoid, adenosine, and glutamate receptors reside. Adenosine, by activating the A1 receptor, reduces the efficacy of THC and other cannabinoids at CB1. And this partially suppresses cannabinoid-mediated LTD, thereby enhancing short-term memory.

But caffeine blocks A1 receptors. This amplifies the impact of cannabinoid activity and, in turn, will lead to greater LTD and temporary impairments in working memory. [6]

CB1 and A1 receptors also exist on GABAergic neurons in the hippocampus. A1 plays a similar gatekeeping role for CB1 in these neurons (it impedes CB1’s suppression of the inhibitory neurotransmitter GABA). GABAergic neurons act as the major brake slowing glutamate release in the hippocampus. [7]

By engaging the CB1 receptor, cannabinoids can promote either LTD or LTP under different circumstances. LTD appears to be more common. Adenosine acting at A1 receptors will enhance memory by reducing LTD. These complex interactions and feedback loops provide neurons with subtle means to fine-tune the brain.

CBD and adenosine




Cannabidiol does not directly activate CB1, but exerts effects through many other pathways. For example, high doses of CBD elevate adenosine levels in the brain by preventing the reuptake of adenosine. This may account for CBD’s ability to ameliorate the short-term memory impairments attributed to THCin some studies. It could be one of many mechanisms that contribute to the “ensemble effect,” whereby the variety of compounds in cannabis can mitigate each other’s side effects and promote each other’s efficacy.

Adenosine is not just a neurotransmitter; it is also known to have intrinsic anti-inflammatory effects. Its reuptake is the main way the body terminates adenosine signaling. Cannabidiol is protective in some models of heart attack, multiple sclerosis, lung injury, and retinal problems because CBD indirectly activates (via adenosine reuptake inhibition) A2A and A1 receptors.

The sedative side effect of high doses of CBD might also be related to amplified adenosine. In clinical trials of a sublingual CBD isolate called Epidiolex, sedation is one of the most common side effects. Although the molecular cause of this is not known with certainty, a high dose of CBD may augment adenosine signaling and contribute to tiredness.

When mixed with caffeine, CBD’s effects on adenosine would probably be dwarfed by caffeine’s antagonistic activity at adenosine receptors. The extent to which this might diminish CBD’s medicinal properties is unknown. Given cannabidiol’s many modes of action, it is unlikely that this would be seriously problematic. But as of now, there aren’t clear advantages to combining or marketing CBD and caffeine together.

Adrian Devitt-Lee is a Project CBD contributing writer.

Footnotes

1. The role of THC and CB1 in fat metabolism is not fully understood. At a cellular level, peripheral CB1receptor activation decreases the metabolism of fat. And cannabinoids, of course, are known to cause the munchies. But cannabis use in the general population is associated with lower rates of metabolic syndrome (type 2 diabetes, obesity, and related complications).
2. Caffeine is broken down to other active chemicals, so altering the metabolic pathway may not simply increase the stimulant effect. As well, cannabinol (CBN), which is formed when THC is broken down by exposure to sunlight or heat, was 30-100 times more potent in blocking metabolism than either CBD or THC.
3. Adenosine, in addition to playing a role in neurotransmission, forms the chemical backbone of cAMP and the related molecule ATP (adenosine triphosphate). ATP is the cell’s chemical battery.
4. Tonic activity occurs when adenosine is constantly released in small concentrations, meaning that A1 is always activated to some degree. Other receptors are constitutively active, meaning they sometimes “turn on” even in the absence of an agonist. In the absence of receptor activity, an inhibitor has no effect. But when a receptor is tonically or constitutively active, antagonists can lower receptor activity to a level below normal. Such drugs are called “inverse agonists,” to distinguish them from “neutral antagonists” that decrease receptor activity to normal, but not lower than normal. Interestingly, this is one reason why animal studies of cannabinoids don’t always hold up across different species. Even mice and rats have different tonic concentrations of adenosine in the brain.
5. The endocannabinoid system promotes homeostasis and is rarely one-directional. Although it generally increases LTD, which weakens synapses to allow other synapses room to grow stronger, it can also do the reverse. In chronically stressed animals where LTP was reduced, CB1 activation restored plasticity by promoting LTP.
6. Although CB1 receptors exist on presynaptic neurons, A1 receptors are expressed on both the pre- and postsynaptic neurons. On the presynaptic side, A1 reduces the efficacy of CB1. But on the postsynaptic side, A1 is inhibitory and opposes the effect of glutamate. By inhibiting postsynaptic A1, the neuron may become more excitable, cascading to endocannabinoid release and even greater activation of presynaptic CB1receptors. Hence, adenosine may be dually inhibiting CB1 activity in this specific set of hippocampal neurons.
7. Beyond the hippocampus, cannabinoids affect memory in a brain region called the amygdala. The amygdala is involved in emotional memories, particularly fear. Research has suggested that without CB1receptors in the amygdala, animals are unable to forget fearful memories. The second adenosine receptor subtype, A2A, is known to be involved in memory as well. In the amygdala, decreased A2A levels are associated with greater fear extinction, suggesting that A2A may play a role in inhibiting CB1 signaling. These interactions, however, have not been studied as of yet. Neither are there studies on how caffeine and cannabinoids interact in their regulation of fat metabolism or the physiological stress response.



Sources

Abush H, Akirav I. Cannabinoids ameliorate impairments induced by chronic stress to synaptic plasticity and short-term memory. Neuropsychopharmacology. 2013;38(8):1521-1534.

Carrier EJ, Auchampach JA, Hillard CJ. Inhibition of an equilibrative nucleoside transporter by cannabidiol: A mechanism of cannabinoid immunosuppression. Proc Natl Acad Sci. 2006;103(20):7895-7900.

Chevaleyre V, Castillo PE. Heterosynaptic LTD of hippocampal GABAergic synapses: A novel role of endocannabinoids in regulating excitability. Neuron. 2003;38(3):461-472.

Durst R, Danenberg H, Gallily R, et al. Cannabidiol, a nonpsychoactive Cannabis constituent, protects against myocardial ischemic reperfusion injury. Am J Physiol Circ Physiol. 2007;293(6):H3602-H3607.

Gonca E, Darici F. The Effect of Cannabidiol on ischemia/reperfusion-induced ventricular arrhythmias: The role of adenosine A1 receptors. J Cardiovasc Pharmacol Ther. 2015;20(1):76-83.

Hampson RE, Miller F, Palchik G, Deadwyler SA. Cannabinoid receptor activation modifies NMDA receptor mediated release of intracellular calcium: Implications for endocannabinoid control of hippocampal neural plasticity. Neuropharmacology. 2011;60(6):944-952.

Hoffman AF, Laaris N, Kawamura M, Masino SA, Lupica CR. Control of Cannabinoid CB1 Receptor Function on Glutamate Axon Terminals by Endogenous Adenosine Acting at A1 Receptors. J Neurosci. 2010;30(2):545-555.

Liou GI, Auchampach JA, Hillard CJ, et al. Mediation of cannabidiol anti-inflammation in the retina by equilibrative nucleoside transporter and A2A adenosine receptor. Investig Ophthalmol Vis Sci. 2008;49(12):5526-5531.

Mijangos-Moreno S, Poot-Aké A, Arankowsky-Sandoval G, Murillo-Rodríguez E.
Intrahypothalamic injection of cannabidiol increases the extracellular levels of adenosine in nucleus accumbens in rats. Neurosci Res. 2014;84:60-63.

Panlilio L V., Ferré S, Yasar S, Thorndike EB, Schindler CW, Goldberg SR. Combined effects of THC and caffeine on working memory in rats. Br J Pharmacol. 2012;165(8):2529-2538.

Peterfi Z, Urban GM, Papp OI, et al. Endocannabinoid-Mediated Long-Term Depression of Afferent Excitatory Synapses in Hippocampal Pyramidal Cells and GABAergic Interneurons. J Neurosci. 2012;32(41):14448-14463.

Shoshan N, Segev A, Abush H, Mizrachi Zer-Aviv T, Akirav I. Cannabinoids prevent the differential long-term effects of exposure to severe stress on hippocampal- and amygdala-dependent memory and plasticity. Hippocampus. 2017;27(10):1093-1109.

Sousa VC, Assaife-Lopes N, Ribeiro JA, Pratt JA, Brett RR, Sebastião AM. Regulation of hippocampal cannabinoid CB1 receptor actions by adenosine A1 receptors and chronic caffeine administration: Implications for the effects of Δ9-tetrahydrocannabinol on spatial memory. Neuropsychopharmacology. 2011;36(2):472-487.

Yamaori S, Kushihara M, Yamamoto I, Watanabe K. Characterization of major phytocannabinoids, cannabidiol and cannabinol, as isoform-selective and potent inhibitors of human CYP1 enzymes. Biochem Pharmacol. 2010;79(11):1691-1698.

ESPRESSO & CANNABIS R necessary on THE PALE DOT we members exist on?
FACTS R refreshing!
before 12 am ESPRESSO work’s 4. Me?
I gave up drugs!
COFFEE & CANNABIS = CIVILIZED & NATURAL + READING is ENHANCED
 
Last edited:

Madri-Gal

Well-Known Member
I used to rely on coffee, but feel much better after I stopped. I am no longer held hostage to caffeine in the morning and can be active immediately upon waking up.
Isn't that wonderful?! I'm so pleased giving up coffee is working out for you. It's quite remarkable when giving up one of one's little habits can lead to such rewards. Now, I myself still enjoy a cup of coffee in the morning. Rarely do I drink the entire cup, but the warmth from the cup is lovely in my hands, and I do enjoy the flavor quite a bit. It comes in handy once a year when deciding what to give up for Lent, because, well, it can't always be chocolate or else it just becomes the annual chocolate hiatus.
 

Diggy Smalls

Well-Known Member
Tea provides me much of the same effect with less caffeine (sometimes none at all) that coffee did without the negatives. As a side note, I was buying a lot of prepared cups of coffee throughout the week to help me keep energy levels up so I wouldn't get trampled by the small children I work with lol. So it's been easier on my finances since I was getting fancy chilled premade coffee drinks and fancy hot coffee from local shops that taste good. I didn't enjoy just any old coffee, I've got refined tastes. lol
 

ataxian

In a BLACK HOLE!
Isn't that wonderful?! I'm so pleased giving up coffee is working out for you. It's quite remarkable when giving up one of one's little habits can lead to such rewards. Now, I myself still enjoy a cup of coffee in the morning. Rarely do I drink the entire cup, but the warmth from the cup is lovely in my hands, and I do enjoy the flavor quite a bit. It comes in handy once a year when deciding what to give up for Lent, because, well, it can't always be chocolate or else it just becomes the annual chocolate hiatus.
I have TEA (green) is has caffeine.
It’s not my choice as my ESPRESSO machine died a horrible death after our last brown out.
I normally have ESPRESSO when I get up.
My youngest & wife have tea so have it as well 2-B social.
2-day I will organize my CANNABIS storage 2-B CIVILIZED
Then I plan 2 reward myself with a session of CANNABIS.
My tea is still hot?
 

Madri-Gal

Well-Known Member
I have TEA (green) is has caffeine.
It’s not my choice as my ESPRESSO machine died a horrible death after our last brown out.
I normally have ESPRESSO when I get up.
My youngest & wife have tea so have it as well 2-B social.
2-day I will organize my CANNABIS storage 2-B CIVILIZED
Then I plan 2 reward myself with a session of CANNABIS.
My tea is still hot?
Is it?
I wonder how tea relates to CANNABIS?
U R social, I'd say.
I enjoy what you say
And the way you say it.
Does CANNABIS work better 4 U without ESPRESSO?
Or is it same?
 

ClearBlueLou

Well-Known Member
Interesting things, metabolites. They result from compounds breaking down into other compounds. Finding that caffeine correlates to lowered levels of cannabinoid metabolites doesn’t suggest depletion of cannabinoids but the opposite, a cannabinoid-sparing action. This directly suggests that caffeine spares cannabinoids from breakdown, preserving their actions as higher-chain compounds.
 

ataxian

In a BLACK HOLE!
So I should vape before coffee? Let the vapor get a head start, I say.
FACTS R ESPRESSO!
I TOOK the drugs you gave up!
Reading isn't natural?
Let me rattle da cage!
ESPRESSO & COLAS go 2- gether?

GRAHAM HANCOCK & RANDALL CARLSON I have been following.
HANCOCK new book is amazing?
CANNABIS helps me read!
Maybe we all react different?
Or is it what U R vaping?
 
Last edited:

ataxian

In a BLACK HOLE!
have never enjoyed the flavor or effects from coffee. SO needs 3 cups or so a day to function.

makes me sweat and my anxiety is through the roof lol


but coffee is socially acceptable. oh well
We R all different?
Espresso with my 1st vaping session help’s!
After 10am I cut the coffee and just vape?
We R all different?
CANNABIS is safer than coffee!
 

ClearBlueLou

Well-Known Member
The US. We bullied the rest of the world into it, basically. Carrot, stick, you name it.

Let me rattle da cage!
ESPRESSO & COLAS go 2- gether?

GRAHAM HANCOCK & RANDALL CARLSON I have been following.
HANCOCK new book is amazing?
CANNABIS helps me read!
Maybe we all react different?
Or is it what U R vaping?
New Hancock - Magicians of the Gods? Newer?
I’ve read a number of his.

Randall Carlson I know by reputation, we’ve had many friends in common of the years but have not met.
He and I have common interests.
 

Sponsored by

PuffItUp Dynavap VGoodiez 420EDC Dispensr
Top