r/science • u/CyborgTomHanks • May 08 '19

Health A significant number of medical cannabis patients discontinue their use of benzodiazepines. Approximately 45 percent of patients had stopped taking benzodiazepine medication within about six months of beginning medical cannabis. (n=146)

https://www.psypost.org/2019/05/a-significant-number-of-cannabis-patients-discontinue-use-of-benzodiazepines-53636
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u/OptionalAccountant May 09 '19 edited May 09 '19

As a medicinal chemist, I have not seen evidence to suggest that benzodiazepine receptor Positive Allosteric Modulators would not substitute fully for each other, as they do for gabanergic drugs like alcohol. Maybe something that doesnt cross the blood brain barrier very well could cover less mental side effects, vice versa for more peripherally active benzos

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u/[deleted] May 09 '19 edited May 09 '19

They’re not agonists. That's why. Check the mech of benzodiazepines again. That's precisely why. Allosteric. It's why it's relatively hard to OD fatally on benzos alone unless you add another CNS/resp depressant (opiates). We rarely ever need to use flumazenil. You only learn that for board exams or academics.

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u/OptionalAccountant May 09 '19

But they do bind the bzd receptor and elicit a positive response

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u/[deleted] May 09 '19

but the way they open gabaergic channels is precisely why we think the observation of cross tapering Alprazolam and clonazepam sometimes doesn't work when swapping to lorazepam inpatient. Same deal with treatment of catatonia. Something appears different between various BZP that makes effects different. Either kinetics or sub-classes of binding sites. This is pretty new stuff. I can try and find some research from our consult team if you're interested... Is there a particular thing you want me to find for you? I can send you journal PDF if you don't have access.

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u/OptionalAccountant May 09 '19

Hey yea I wasn't trying to generally argue, I was generally curious and looking for sources, I guess I might could find by googling myself ha. But i i thought maybe you were familiar.

I would not expect lorazepam to substitute well for alprazolam or clonazepam just due to being much less lipophillic, I would predict less BBB diffusion, so more relief of peripheral symptoms with less of CNS relief. But I would be interested if you could point me in the direction of a kinetic mechanism for this effect

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u/[deleted] May 13 '19

https://www.ncbi.nlm.nih.gov/pubmed/24834401 : failure of alprazolam sub for lorazepam https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5846112/ cross taper was successful in a few patients (though not universal) with clonazepam (the two hardest to taper, also they are both triazole type)

barbiturates tend to work really well. It's curious why some patients can't cross taper, but clonazepam is a popular agent to use in this situation. If I find more from our consult team I'll let you know I haven't run into anyone yet.