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Bupe SHOULD block the effects of Pot but doesnt....why?

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daddysgone

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Joined
Oct 22, 2007
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From several sources (including our fave, Wiki) it has been stated that the effects of THC and related cannabanoids can be "suppressed by the CB1 cannabinoid receptor antagonist rimonabant (SR141716A) as well as opioid receptor antagonists".

Since bupe acts as a mixed partial agonist/antagonist, one would think there would be at least partial blocking of the effects from marijuana. However in my experience, and the experience of others ive spoken with, this does not seem to be the case. Bupe does not seem to block marijuanas effects at all from what i can tell.
Any ideas as to why this particular agonist/antagonist does not block the effects of marijuana. To be honest, I am somewhat surprised to read that opioid antagonists are believed to block MJ's effects-I know that MJ does somehow engage the opioid pathways, but im fairly certain that is only partially responsible for the effects of marijuana. Anyone have any ideas?
 
anyone i knew on suboxone got REAL fucked up when they smoked weed. like a bowl would have them higher than a bowl should get you.
 
tripmonkey505 said:
anyone i knew on suboxone got REAL fucked up when they smoked weed. like a bowl would have them higher than a bowl should get you.
Click to expand...

yes, i agree. if anything, it seems the combo of bupe/MJ is MORE potent then the sum of their parts. This is what prompted me to make this thread. On paper, one would expect bupe (acting effectively as an antagonist) would at least partially block the effects of MJ, but in real life, this just doesnt seem to be the case.
 
If Buprenorphine were such a drug that having taken it one experienced dysphoria rather than euphoria, then it would be sensible to conclude that it should at least partially block the effects of cannabis. However, Buprenorphine, while not a full agonist, is still an agonist - enough that it produces euphoria and enhances the effects of cannabis. To speak with technical inaccuracy, but nevertheless in such a way as to facilitate understanding, buprenorphine produces a net increase in mu-opioidergic neurotransmission (it's actually probably depression of neurotransmission which opioids produce, through a decrease in the rate of cAMP synthesis).
 
Buprenorphine is an antagonist only on kappa receptors.
 
dread said:
Buprenorphine is an antagonist only on kappa receptors.
Click to expand...

no, i dont think this is entirely correct. I thought that due to bupe's extremely high binding affinity at mu, it effectively acts as an antagonist for other opioid agonists. am i wrong about this?
 
Even if it did block mj's effects, it wouldn't do it entirely. Maybe the opioid euphoria ([+]mu=[-]gabab=[+]DA) is replaced by the buprenorphines. who knows.
 
daddysgone said:
no, i dont think this is entirely correct. I thought that due to bupe's extremely high binding affinity at mu, it effectively acts as an antagonist for other opioid agonists. am i wrong about this?
Click to expand...

What does it matter which substance is responsible for the activation of the mu opioid receptors? Marijuana has various components to it; one of those is activation of mu-opioid receptors (allosterical activation). As long as that is present to a certain degree or beyond, whether or not the marijuana is responsible for it, one is going to have a subjective experience very similar or identical to that produced by marijuana alone.

Since buprenorphine far more potently activates MORs, it stands to reason that taking marijuana and buprenorphine together would give you a marijuana high with stronger feelings of euphoria and relaxation, but with feelings of nausea possibly.
 
Hi daddysgone,

The systems at play are SO MUCH more complex than that, that researchers have even found it possible to largely recreate the effects of opioid agonists using nothing more than serotonin modulation systems (closed loop) on mU knockout mice. And keep in mind, mice are far more simple than man! What I'm trying to say, it doesn't surprise me one bit. Why not? Because there are far more (hypothetically) perplexing neurotransmitter phenomena, and yet, there is no arguing the apparent results.

Did you know, many of the effects of simple halogenated alkanes and alaphatic/aromatic solvents, are postulated to be partially opioid mediated? That's right, Duster and toluene. Even GHB's effects can somewhat be reversed by naloxone challenge. But then again, there are agents which are CLEARLY mu agonists, for which naloxone/naltrexone pose no competition. And there are morphine derived agonists (FULL agonists) incorporating the tert-N-cyclopropyl methyl (the same moiety which gives naltrexone it's antagonistic effect). Like NIH11151. We've barely scratched the surface, so you shouldn't be surprised, as there is much more surprising than that.
 
Even someone on naloxone or naltrexone will still get high if they smoke. These will probably block some of the euphoria and analgesia produced by the CB1 agonist, but it won't impact the hallucinogenic effects- just as you can still get drunk from ethanol on naltrexone but will lack the euphoria.

The title should be "Buprenorphine SHOULD NOT block the effects of cannabis, and doesn't"
 
dread said:
Buprenorphine is an antagonist only on kappa receptors.
Click to expand...

I'm curious to know about the interactions of buprenorphine at the sigma receptor, as I feel that it (extremely low-dose) may have interacted with an administration of DMT recently.
 
Buprenorphine has little or no sigma affinity.

Sigma receptors have preference for the opposite isomer as mu-receptors. Dextro-morphinans may be sigma agonists, but they will have no or virtually no affinity for mu receptors. Levo-morphinans, on the other hand, will be the exact opposite.
 
Sub lingual ingestion of Suboxone coupled with the smoking of cannabis Sativa(and sometimes indica) enabled me to quit a few year Heroin addiction & become the semi-function able kinda contributing member of society i am today! Seriously though most my family thought id die but that combination did wonders(possibly treating anxiety & such that lead to addiction?).
 
tripmonkey505 said:
anyone i knew on suboxone got REAL fucked up when they smoked weed. like a bowl would have them higher than a bowl should get you.
Click to expand...

Thats because that person still got high from bupe. A smaller bupe dose for someone who isnt as opiate naive (where the bupe would have just blocked the opiate effects), the bupe would have inhibited the weed effects. Weed effects arent only mu angonism mediated though, there are plenty of things that happen in terms cb1 agonism effects that inhibit GABA release (which then up-regulates a few other things). Bupe might just make the high less physical and more mental.
 
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