Why does marijuana have different effects for different ROAs??

[red_bandit]

I've never been much of a pot smoker because it almost always makes me super-anxious. Apparently, lots of people react this way. If I eat it, though, I have the exact opposite reaction. It decreases anxiety, makes me a little sleepy, and just generally makes me feel awesome. Same substance. Different ROAs. Completely opposite physical/mental effects?

Today I thought of a plausible explanation for it. This must have already been thought up so I apologize if I'm re-inventing the wheel (please point me in the direction of that information if you know)...

Endogenous cannabinoid signaling by CB₁-receptor activation is known to potently depress the release of GABA from inhibitory cells. THC similarly binds to CB₁ and activates cannabinoid-mediated inhibition of presynaptic GABA release. Less GABAergic inhibition obviously means more excitation. I'm pretty sure that this happens in the amygdala which would lead to anxiety.

Apparently, THC degrades to cannabinol pretty easily when exposed to light and air and, presumably, when ingested. Cannabinol is has virtually no psychoactive effects. So the ingested THC would basically become inert and the effects another cannabinoid called cannabidiol dominate. Cannabidiol interacts with a couple of different receptors, one of which is the predominate serotonin receptor in the brain, 5-HT_1a, where it acts as a partial agonist and BOOM! The chilled out serotonergic effects are stronger when effective THC concentrations are low.

So...

Smoking fresh nugs --> THC levels are higher than other cannabinoids in the brain --> THC activates CNS-specific CB₁ cannabinoid receptors --> Presynaptic inhibition of GABA release --> decreased iinhibition/increased excitation (especially in regions involved in fear responses, like amygdala) --> increased anxiety??

Eating tasty goods --> THC degrades to inactive cannabinol --> levels of cannabidiol exceed those of THC in the brain --> cannabidiol activates 5-HT_1a receptors --> increased serotonergic activity --> decreased anxiety/enhanced mood??


The "low-hanging fruit" experiment would be for me to smoke some from a low-THC strain. If I'm right, I should get effects similar to eating a higher THC strain.

::sigh::

Sure do wish I lived in a medical MJ state right now.

Actually, I'm always wishing I lived in a medical MJ state...

Thanks for your input!

 

[pasha]

Homeless -> Advanced Drug Discussion

 

[AlphaMethylPhenyl]

If I eat it, though, I have the exact opposite reaction.

Apparently, THC degrades to cannabinol pretty easily when exposed to light and air and, presumably, when ingested. Cannabinol is has virtually no psychoactive effects. So the ingested THC would basically become inert and the effects another cannabinoid called cannabidiol dominate.

Thanks for your input!

I'm assuming that first statement was an exaggeration.

Cannabidiol has been all but bred out of most strains.

While most find eating cannabis-infused food gives more of a physical feeling than eating it, psychological overdose more often occurs when ingested. And ingested cannabis (assuming its de-carboxylated) is frequently described as being more psychedelic, or hallucination-provoking, than smoked. If 5-ht1a agonism were responsible for this we'd see people tripping out on buspar, notwithstanding negligible CBD content.

http://jop.sagepub.com/content/26/10/1333.short

cb2 agonists are underestimated:
http://onlinelibrary.wiley.com/doi/...sCustomisedMessage=&userIsAuthenticated=false

What makes a scary movie scary? The sudden introduction of stimuli.

 

[sekio]

THC does not degrade to cannabinol that easily... it takes months and months in heated storage. It certainly does not get degraded to cannabinol in biological systems upon ingestion, like you suggest.

the reason for different effects is probably increased metabolic conversion of THC to 11-OH-THC and related cmpds in the liver when orally ingested. 11-oh-thc is a more potent cb1 agonist than THC is.

also, how quickly the drug builds in concentration is an important factor in the biological response (c.f. oral cocaine/methylphenidate versus smoking crack rocks). oral thc is very slowly absorbed compared to the 15-60 seconds it takes for inhaled thc to reach peak concentrations after a hit

Clarke's suggests that oral cannabis/THC is less than 50% of the bioavailibility of smoked cannabis, too.. so that probably plays a role, as well.

 

[Psychedelic Jay]

THC does not degrade to cannabinol that easily... it takes months and months in heated storage. It certainly does not get degraded to cannabinol in biological systems upon ingestion, like you suggest.

the reason for different effects is probably increased metabolic conversion of THC to 11-OH-THC and related cmpds in the liver when orally ingested. 11-oh-thc is a more potent cb1 agonist than THC is.

also, how quickly the drug builds in concentration is an important factor in the biological response (c.f. oral cocaine/methylphenidate versus smoking crack rocks). oral thc is very slowly absorbed compared to the 15-60 seconds it takes for inhaled thc to reach peak concentrations after a hit

Clarke's suggests that oral cannabis/THC is less than 50% of the bioavailibility of smoked cannabis, too.. so that probably plays a role, as well.

I was about to say the same thing on the speed and height of blood concentrations...


What causes it to provoke so much anxiety? I never understand that.

One day or years a person is completely fine, then that one special panic attack occurs... Most don’t smoke anymore after that...

 

[bolinas]

Two overlooked effects on smoking vs eating:

1. Pyrolysis breaks down the psychoactives into other chemicals. These other chemicals have different effects.

2. Smoking high grade pot, cocaine, smoking anything floods the receptors much quicker and has a different effect than eating it. More addictive, for sure.

I have no idea what the technical explanation is, but it seems to me that repeatedly flooding the receptors with a chemical to their limit, over and over, has more negative side effects than eating. This is especially true with the synthetic cannabinoids. They are GREAT orally, dissolved in oil. Longer lasting with little paranoia unless you go to extreme doses. They are a disaster smoked, short lasting, odd side effects, high paranoia...

 

[Elven Warriorr]

Whenever cannabis is drank, it has a very low psychoactivity in comparison to it's other ROAs, which is mainly because THC is not water soluble. However, when cannabis is consumed through eating, for some reasons which I'm not exactly sure about, it contains more THC than when it's either smoked or drank. This may because smoking destroys some of it's psychoactive properties, but not as much as what water does.