Bupe Buprenorphine and cannabis interaction, clinical study

[papercuts]

I've noticed that going a day without vaping any bud makes me sick, physically as well as cravings. I don't think it was that way before I started on a steady dose of Bupe in 2020, hard to know.

So I found this small study of only 32 peeps;

Buprenorphine–cannabis interaction in patients undergoing opioid maintenance therapy - European Archives of Psychiatry and Clinical Neuroscience

Buprenorphine is a partial μ-opioid agonist widely used for opioid maintenance therapy (OMT). It is mainly metabolized to pharmacologically active norbuprenorphine by the cytochrome P450 (CYP) isozyme 3A4. This may give rise to drug–drug interactions under combinations with inhibitors or...

link.springer.com

The sample size is a concern, but the findings are interesting, basically you will have maybe three times the bupe in your system if you also consume cannabis, then quitting cannabis will cause bupe levels to drop back down and there is a case report half way down that sounds familiar to me. The guy had some opiate wd from stopping cannabis.

Anyone else here on a steady dose of bupe and also partial to some bud, what do you think?

 

[papercuts]

This quote sums it up;

"The pharmacokinetic interaction may give rise to enhanced or altered opioid activity and risk of intoxications. Physicians should inform patients about this risk"

I agree, I would have found this information useful.
Can I be a fly on the wall when those physicians get told they have to tell their opiate dependant patients how to triple the effects of their meds?

 

[G_Chem]

This is very interesting, maybe why I’ve always needed far less than others because I smoke cannabis all the time. When I refrain from smoking I definitely feel like I need more Suboxone but I wrote that off as just cannabis withdrawal.

I just felt my body was very dependent on cannabis but now that I know this maybe the times where I quit cannabis and had intense opiate wd like symptoms it was because of this. I never had that before, but it’s hard to remember the before time. I only smoked cannabis 3 or so years before getting addicted to opiates.

Good find!

-GC

 

[papercuts]

This is very interesting, maybe why I’ve always needed far less than others because I smoke cannabis all the time. When I refrain from smoking I definitely feel like I need more Suboxone but I wrote that off as just cannabis withdrawal.

I just felt my body was very dependent on cannabis but now that I know this maybe the times where I quit cannabis and had intense opiate wd like symptoms it was because of this. I never had that before, but it’s hard to remember the before time. I only smoked cannabis 3 or so years before getting addicted to opiates.

Good find!

-GC

In a good many years of cannabis consumption in many forms, I don't remember having any physical symptoms other than appetite changes, dry eyes and mouth, that's it, I don't even notice pain relief from it. Then since starting on bupe I can't take a day off it without getting opioid like withdrawal symptoms. It took me until now to believe myself on this. At first I was blaming the strains.
Always been a stop start toker, few years, months, days, whatever, then some time without.
Never was a problem before.

 

[Skorpio]

This paper rips into the notion that cannabis is inert when it comes to drug-drug interactions.

I hope to see better pharmacological studies on cannabis + other drug combinations as prohibition crumbles ("what is CYP3A4?" might be what if blurt out if i saw the jeopardy question "this is the most significant enzyme for drug metabolism").

It also makes me wonder if something like grapefruit juice would extend the duration of cannabis (i am going under the assumption that the cannabinoids are competitive inhibitors, not mechanistic inhibitors, could be wrong, but i don't see too many "alert" moieties that predispose to mechanistic inhibition).

 

[Xorkoth]

So cannabis increases the effectiveness of bupe? I'm on the end of a relatively quick taper, down to 2mg left, planning to take 0.5mg the next 2 days and then 0.25mg the next 4 days. I don't usually use cannabis these days but I am pretty tempted right now. Not really looking forward to this next stretch.

 

[papercuts]

I did a search for what else might have a cannabis like interaction and got grapefruit and goldenseal. Found this about goldenseal;

Given the convincing evidence that goldenseal inhibits CYP3A4, it is likely that goldenseal inhibits the metabolism of other CYP3A4 substrates such as alfuzosin, calcium channel blockers, carbamazepine, colchicine, ergot alkaloids, phosphodiesterase inhibitors, ranolazine, vinca alkaloids, and selected members of other classes, such as benzodiazepines, statins, corticosteroids, opioid analgesics, antipsychotics, antiarrhythmics, antidiabetics, and protease inhibitors.

I know statistics enough to think the tests used were reasonable and show very strong evidence of a significant interaction, but I don't know chemistry.

Can anyone tell me what the effect of having 21 times the level of bupe in your blood is when the norbuprenorphine wasn't affected conclusively at all?
Which one attaches to receptors and works? No, forget that, I just remembered the article says bupe is much more effective than norbupe, that answers it adequately.

A lot of potential meds implicated there.
So while I'm on bupe, high on my list of meds for giving up cannabis will be goldenseal and grapefruit. I'll report back here if it works.

 

[papercuts]

So cannabis increases the effectiveness of bupe? I'm on the end of a relatively quick taper, down to 2mg left, planning to take 0.5mg the next 2 days and then 0.25mg the next 4 days. I don't usually use cannabis these days but I am pretty tempted right now. Not really looking forward to this next stretch.

Tell me about it, I thought I was at 0.5mg per day, I also thought it odd that whenever I've had an extra 1 or 2mg, it has very little effect, nothing very noticeable. If I have 21 times the level in my blood like the guy in the case report, then I might as well be taking 10.5mg a day then not noticing an extra 1 or 2mg makes a lot more sense.

No wonder life without cannabis becomes impossible. The guy in the study went from 6.3mg/L to 0.3mg/L of buprenorphine in his bloodstream, just from stopping cannabis. No wonder we're getting opioid withdrawal symptoms.

I'm a bit gobsmacked that the interaction is that strong. I'm fucking gutted that I'm probably nowhere near the low level of bupe I thought was in my system and have no way of knowing what level I'm at.

 

[Xorkoth]

Case report​

One patient in long-term OMT who was followed in this study since 2012 being clinically stable and in long-term employment ever since presented with marked clinical decline. He had always been using cannabis while on OMT with no additional concomitant drug use and required gradual increases in buprenorphine dosage from 7 to 10 mg daily over a course of 6 years starting 2012. This was consistent with increasing physical requirements by his occupation. He did not require any medication except for a pregabalin prescription (300 mg/d) which is not known to interfere with buprenorphine or cannabis metabolism. At one presentation, he reported sleep disturbances, agitation and decreased motivation, drive, contemplation and overall mood. Affect lability was found to be increased, and a depressive episode was diagnosed. Furthermore, the patient reported he had quit cannabis use a month ago, and this was confirmed by immunologic urine analysis and serum GC/MS for THC and metabolites (serum THC < 0.5 ng/mL, THC-COOH < 2.5 ng/mL, 11-OH-THC < 0.5 ng/mL) compared to presentation 6 months earlier (THC 16.82 ng/mL, THC-COOH 28.46 ng/mL, 11-OH-THC 1.63 ng/mL). He reported improved feeling of somatic health but increasing psychological issues. Upon clinical observation, he appeared pale, sweaty and agitated, indicating a withdrawal syndrome. The patient reported severe buprenorphine craving; this prompted buprenorphine status evaluation. Indeed, both buprenorphine and norbuprenorphine levels were markedly decreased compared to presentation six months earlier (0.3 ng/mL vs 6.3 ng/mL for buprenorphine; 0.3 ng/mL vs 1.0 ng/mL for norbuprenorphine), metabolic ratio having increased (1.00 compared to 0.16 6 months earlier).

(emphasis mine)

Holy crap, that really IS a huge difference. 0.3ng/mL vs 6.3ng/mL.

I've taken a THC chocolate, and once it kicks in I am going to take my 0.5mg of suboxone as planned today. I'll see if I notice a difference. Notably, this is my first day taking 0.5mg, yesterday and the day before I took 1mg. So presumably I should feel it less than yesterday, but it may be that I will feel it substantially more. Which is what I hope. Though such a thing might negatively impact the taper. But... yeah I don't feel very good and I want to feel good. Plus, science.

It's only a 10mg chocolate because since I don't really use cannabis much at all anymore, I'm a lightweight now and it gives me anxiety easily.

 

[G_Chem]

(emphasis mine)

Holy crap, that really IS a huge difference. 0.3ng/mL vs 6.3ng/mL.

I've taken a THC chocolate, and once it kicks in I am going to take my 0.5mg of suboxone as planned today. I'll see if I notice a difference. Notably, this is my first day taking 0.5mg, yesterday and the day before I took 1mg. So presumably I should feel it less than yesterday, but it may be that I will feel it substantially more. Which is what I hope. Though such a thing might negatively impact the taper. But... yeah I don't feel very good and I want to feel good. Plus, science.

It's only a 10mg chocolate because since I don't really use cannabis much at all anymore, I'm a lightweight now and it gives me anxiety easily.

I eat edibles pretty often, use tincture every night, and I can still feel 10mg pretty darn good. Interested to hear the results

Yea this thread has been a bit of a kick in the nuts, if this is true then I too could be at a much higher blood level than I realize..

-GC

 

[Xorkoth]

I haven't noticed any increase in potency, in fact I have felt shivery and somewhat anxious all day. I ended up taking an extra 0.25mg and I feel better now. But less bupe left to taper... oh well. I have kratom.

 

[papercuts]

I haven't noticed any increase in potency, in fact I have felt shivery and somewhat anxious all day. I ended up taking an extra 0.25mg and I feel better now. But less bupe left to taper... oh well. I have kratom.

It sounded like chronic daily use and that builds up in your system over time, at first I thought, "wow, great" then I tthought about it and went, "Ah shit" because i realised i was basically fucked.

I asked a question a few months ago on BL, maybe in cannabis discussion.
I was going from amnesia haze (22% ) to some 14% shit and I was still getting symptoms like mild withdrawal a month or something after. Now I'm good on more 20+%.

Maybe some strains interact more strongly than others which is how it was possible to have symptoms like opioid wd after my ammo haze ran out (I'd about 5 oz off a really nice plant and smoked nothing but that for months)

 

[Xorkoth]

Well I feel quite good now, and also weed high (it took a long time to kick in). I did take more bupe though, but I actually feel quite good which is unexpected.

 

[DeathIndustrial88]

Yes!!!!

I started out on bupe and quit smoking weed for it at the time.
but I eventually went back to smoking. And now it seems like I need some form of THC in order to get my meds to "work" and stop cravings, which bupe hardly does anymore as it is.

Isn't THC an opioid receptor modulator as well? Not totally sure what that means, but I think it means there would be a potentiation effect, which there is.

I also have what feels opioid withdrawals whenever I have to go without THC, where I don't remember having any sort of "withdrawal" when I'd quit smoking before, minus the boredom.

 

[G_Chem]

Since this thread I’ve been keeping my eye on this, yesterday I didn’t smoke much after daily smoking for many weeks. I had to take a slight bit more than normal and still felt sweaty and anxious. I’ve always thought this was cannabis WD but now I’m starting to believe this is indeed lower levels of Bupe.

-GC

 

[headfuck123]

I have found tapering opiates next to impossible without cannabis, this would explain why maybe. Had a rare couple weeks without any cannabis and felt aweful, I just put this down to the tapering.

 

[ĐmantuNJofra]

well bump to make this thread almost a year old, to not open another with just the short observation.
I smoked 10-15 years ago and that was the only drug at that time, for 2-3 years till it just became effect-less!
later when was partying with amps, mdma, coc, ....always made me paranoid!
Started with buprenorphine and pregabalin and while it made me little anxious at the start, I endured it cause I always believed in this plants anti-anhedonic propt.

So I also think that it may be the case with higher levels and this is stretched and just subjective, but I tested it with my psych I showed that to her.
I needed to to that cause of the driving license but I remember that she was holding the paper and red to me before she asked!
She doesn't mind that I smoke and when blood tests came she said: Have you taken 8m in last 2-3 days and did you take some just before test?
I cannot find the paper as my "creative mess" is just a mess now with documents and all! Bt the point is it was higher
I didn't! I took 1mg-on Sunday, 1mg Monday, morning was my blood test and I said: I will take now 1-2 mg sublingual after.

I said my meds just seems to work with THC, we have now CBD-strains, 0,2THC on every news-stand but that's nothing it's BS.
And when I don't have weed I seem to need the next day like 8mg intranasal and it even do just like 2hrs and after I'm just apathetic or anhedonic.

 

[papercuts]

well bump to make this thread almost a year old, to not open another with just the short observation.
I smoked 10-15 years ago and that was the only drug at that time, for 2-3 years till it just became effect-less!
later when was partying with amps, mdma, coc, ....always made me paranoid!
Started with buprenorphine and pregabalin and while it made me little anxious at the start, I endured it cause I always believed in this plants anti-anhedonic propt.

So I also think that it may be the case with higher levels and this is stretched and just subjective, but I tested it with my psych I showed that to her.
I needed to to that cause of the driving license but I remember that she was holding the paper and red to me before she asked!
She doesn't mind that I smoke and when blood tests came she said: Have you taken 8m in last 2-3 days and did you take some just before test?
I cannot find the paper as my "creative mess" is just a mess now with documents and all! Bt the point is it was higher
I didn't! I took 1mg-on Sunday, 1mg Monday, morning was my blood test and I said: I will take now 1-2 mg sublingual after.

I said my meds just seems to work with THC, we have now CBD-strains, 0,2THC on every news-stand but that's nothing it's BS.
And when I don't have weed I seem to need the next day like 8mg intranasal and it even do just like 2hrs and after I'm just apathetic or anhedonic.

Thanks for adding that, I had no numbers to put to anything, your experience makes it seem a huge increase, so the doctor thought you were taking 8mg when you were only on 1mg? Grapefruit is supposed to do something similar, but damn if I didn't forget while I had two months of no bupe at all. I meant to see if a day or two without weed would be physically difficult or if it would go back to being just psychological. I should have a few days off it anyway, the bags under my eyes have whole suitcases of their own, it's not a good look.

 

[DeathIndustrial88]

I asked on BL a year or more ago if "euphoria" or affects of drugs could be dependent on a cannabinoid system. Especially if you've been a long term pot smoker.
Although I don't think anyone really knew.

For example I'll use myself. I've been smoking weed since I was 12. And in the recent years I've started to notice that I couldn't feel my meds the same unless I also smoked weed with them.

Although this isn't exactly what I meant, I do think I was onto something. At least in the case of certain opioids & cannabis. I've always felt like cannabis was the best thing you could find to potentiate your opioid. I started noticing in the recent years that a day on buprenorphine + cannabis were remarkably different than days just on bupe alone.

 

[DeathIndustrial88]

well bump to make this thread almost a year old, to not open another with just the short observation.
I smoked 10-15 years ago and that was the only drug at that time, for 2-3 years till it just became effect-less!
later when was partying with amps, mdma, coc, ....always made me paranoid!
Started with buprenorphine and pregabalin and while it made me little anxious at the start, I endured it cause I always believed in this plants anti-anhedonic propt.

So I also think that it may be the case with higher levels and this is stretched and just subjective, but I tested it with my psych I showed that to her.
I needed to to that cause of the driving license but I remember that she was holding the paper and red to me before she asked!
She doesn't mind that I smoke and when blood tests came she said: Have you taken 8m in last 2-3 days and did you take some just before test?
I cannot find the paper as my "creative mess" is just a mess now with documents and all! Bt the point is it was higher
I didn't! I took 1mg-on Sunday, 1mg Monday, morning was my blood test and I said: I will take now 1-2 mg sublingual after.

I said my meds just seems to work with THC, we have now CBD-strains, 0,2THC on every news-stand but that's nothing it's BS.
And when I don't have weed I seem to need the next day like 8mg intranasal and it even do just like 2hrs and after I'm just apathetic or anhedonic.

This is how I feel on long term bupe, especially without any cannabis or other drugs.
The first 2hrs after taking my buipe consist of just me coming to a feeling of "feeling normal & semi-emotionally stable" and then after that, I'm really tired, apathetic, lethargic & anhedonic. Usually for the rest of the day or until I take a nap.

This perfectly describes the hell of being on buprenorphine. Would be so much better to be able to take a normal shorter acting full agonist everyday instead of living like this.
Taking more bupe doesn't do jack shit either.


It's much more tolerable & not as bad when you're able to compound it with some cannabis.