Is this Clonazepam taper too fast?

Here's the google sheet with the details.  Proposed taper is intended to take me from 1.0 mg Clonazepam qd to 0 mg qd in ~90 days. I would be grateful for any comments and especially suggestions for improving the taper:

 

https://docs.google.com/spreadsheets/d/1OrwvgPR7KNC0cpr6X5TNWNwiiw3je7l9q0eJH78PA-8/edit?usp=sharing

Hello Edgee!

 

I would describe this schedule as a linear taper with an attenuated ending. I suspect you will have problems with this taper schedule. If you don't, you are in the minority around here.

 

For one, a hold taper period of 1 week does not typically allow for a full realization and recovery from a clonazepam cut. The average half-life is 35 hours, which is realized fully over an average 9 days; my cuts typically peaked in WD symptoms between days 5-7, and resolved by days 10-14. These were 6-7%/14 day cuts; had I personally taken larger reductions, the time to recover my full functionality would have likely been much longer.

 

I like your use of an attenuated ending; however, switching to a longer hold time isn't ideal for this purpose. As mentioned, the half-life of clonazepam remains the same throughout the taper. In order to attenuate the ending of your taper, I suggest taking 1/3rd your previous reduction amount for the last 1/3rd of your taper. So since you were reducing linearly at 0.1mg/period, I'm suggesting you reduce to 0.03mg/period to attenuate until the end.

 

Linear tapers, even with attenuated endings, seem to carry an increased risk of severe WD symptoms. Around the forum the general guideline is to use a percent-based taper schedule, and to keep the rate between 5-10%/14 days. Some people can go faster, some need to go much slower. Percent-based reductions, in my experience, are more symptomatically consistent and thus easier with which to maintain functionality.

 

At the minimum, I suggest giving yourself two-week hold times right from the beginning. I think the answer to your topic question will depend entirely on you; specifically your neuroplasticity, over-all health, and history of benzo use. I believe the answer would appear most readily by taking at most a 10% cut, and seeing how your body responds over a two-week period.

 

I notice you are using a 0.1mg/ml solution. If you got yourself a 1ml syringe with 100 gradations you'd have a lot more degrees of accuracy for reducing; your 0.1mg/ml solution could be reduced by any 0.001mgs increments. Smaller, more frequent dosage reductions have given my clonazepam taper significantly reduced symptoms. I take 0.43% reductions daily, and I notice very few withdrawal symptoms.

 

You could do something similar, while still aiming for higher bi-weekly reduction rates, by dividing your reduction goal into smaller parts spread out over the two weeks. This could be daily, or not; what I think this does is ti spreads out the neurological repair work over a longer period, not necessarily speeding up the over-all tolerated rate, but definitely minimizing the rollercoaster of WD symptoms I felt on a cut-and-hold schedule.

 

It's awesome that you have spreadsheet skills. If you'd like to explore a DMT without doing the spreadsheet work yourself, you could take a look at a tool like this:

http://www.benzobuddies.org/forum/index.php?topic=254653.5#post_generator

 

It has the ability to chart a linear taper, like the one you have created, and it will also create an attenuated ending if doing so and desired.

 

I hope this helps. Just some ideas to consider. 

Hi Edgee

 

Would you mind giving some more background info? Your signature shows you've tapered Clon from 3mg to 2mg in the past. That 1mg reduction took you approximately 9 months if I understand correctly. How did you feel during that taper? How long have you been on your current 1mg dose and do you feel stable?

 

As Slow said your suggested taper seems a bit aggressive and linear tapers tend to catch up with you.  As stated above the general consensus is a % and symptoms based taper which relies on 5-10% cut of your current dose every 2 weeks. By cutting on a weekly basis, you're not really allowing your body time to adjust to the new dose because Clon stays in your system for an extended period. How you metabolize the half life of the drug varies per person. My metabolism is very slow and I only know the full effect of a cut around day 9-10.

 

By allowing a 2 week period, it gives your body time to either remain functional or increase wd symptoms. This is the only way to know whether your cuts are acceptable or too big. If I cut on a weekly basis and by day 9 develop increased wd symptoms then I'm already into my second cut. That means rectifying two cuts and you're playing yo-yo with your brain when all your brain is craving is consistency.

 

If you have been stable at this dose for quite some time now, you might be able to get away with bigger cuts at the start. But it would probably be better to test it out over a 2 week period.

 

Ultimately it's up to you to decide what you feel comfortable experimenting with and since this is not the first time you've lowered your dose, you probably know what you're in for.

 

Hi Edgee

 

Would you mind giving some more background info? Your signature shows you've tapered Clon from 3mg to 2mg in the past. That 1mg reduction took you approximately 9 months if I understand correctly. How did you feel during that taper? How long have you been on your current 1mg dose and do you feel stable?

 

Jelly Belly, thanks for your interest.  I've updated my sig to more accurately reflect my benzo history.  By the standards of this forum, I'm coming off a very fast and large reduction in dose--I reduced from 2.5mg Clon to 1.0 mg Clon in six weeks.  So I've been at 1.0 mg for about two weeks now.  I didn't notice any WD symptoms until I hit 1.0mg, but I do notice a large increase in my "oomph"--my energy and initiative to get things done, and my appetite for physical exercise.  At 1.0 mg, I've had three bad days.  I do not feel stable, but I feel a helluva lot better than being a zombie on 2.5 mg Clon.

 

My taper plan came from this scholarly article:

 

https://pubmed.ncbi.nlm.nih.gov/20473065/

 

Here's the gist of the plan I followed:  "The dosage of clonazepam was decreased by 0.5 mg per 2-week period until 1 mg per day was reached, followed by a decrease of 0.25 mg per week."

 

Now that I'm down at 1.0 mg Clon, I don't want to screw up what I accomplished with so little time and effort.  Hence my interest in a more conservative taper to finish the job.

 

 

Hi Edgee

 

Would you mind giving some more background info? Your signature shows you've tapered Clon from 3mg to 2mg in the past. That 1mg reduction took you approximately 9 months if I understand correctly. How did you feel during that taper? How long have you been on your current 1mg dose and do you feel stable?

 

Jelly Belly, thanks for your interest.  I've updated my sig to more accurately reflect my benzo history.  By the standards of this forum, I'm coming off a very fast and large reduction in dose--I reduced from 2.5mg Clon to 1.0 mg Clon in six weeks.  So I've been at 1.0 mg for about two weeks now.  I didn't notice any WD symptoms until I hit 1.0mg, but I do notice a large increase in my "oomph"--my energy and initiative to get things done, and my appetite for physical exercise.  At 1.0 mg, I've had three bad days.  I do not feel stable, but I feel a helluva lot better than being a zombie on 2.5 mg Clon.

 

My taper plan came from this scholarly article:

 

https://pubmed.ncbi.nlm.nih.gov/20473065/

 

Here's the gist of the plan I followed:  "The dosage of clonazepam was decreased by 0.5 mg per 2-week period until 1 mg per day was reached, followed by a decrease of 0.25 mg per week."

 

Now that I'm down at 1.0 mg Clon, I don't want to screw up what I accomplished with so little time and effort.  Hence my interest in a more conservative taper to finish the job.

 

Hi Edgee,

 

I'm so happy for you that your faster taper paid off! It seems like your body is responding similar to mine to a faster taper. I went from 2mg to 1 mg pretty quickly and I can only describe it as severe but tolerable. Then I went from 1mg to 0.5mg. This cut sent me into acute wd where I was not functional at all. When I reinstated it took me 2 days to become functional (get out of bed do basic tasks) and I held for 3 weeks to feel fully functional. My taper and wd has been fairly good in comparison to what others are going through.

 

When I started my DMT and essentially cutting from 1mg, I started from a point of feeling fully functional and stable. I was cutting at the very high end of the recommended % of my current dose every 2 weeks. It was going really well until 5 weeks in when I could feel it catching up. It was not intolerable but I needed more functionality for work. In week 5 I decided to change my dose to 8.7%. I didn't need to hold, I just changed the dose. After 4 days I felt better. It's now been just over 3 weeks on the new dose and I'm doing pretty well.

 

I'm describing my experience because it seems to me that our bodies are reacting similar to wd. You are very sensible to be questioning your taper rate at this point because your body is probably telling you that the rate you've been doing is not sustainable. My suggestion would be that you hold at 1mg until you feel stable before attempting another cut. The main reason for this is that you want to establish a baseline to compare your new cut and symptoms to. If you start cutting too early and you don't feel stable it is difficult to tell whether the symptoms are still residual wd from your big cut overlapping with your new cut, or whether it's only wd from the new cut that's too much for your body.

 

I would recommend that any cut you make, you hold for at least 2 weeks to fully realize the effect of the cut. I would also suggest reducing by a percentage of your current dose rather than a linear taper. These seem to be easier to manage and adjust when you're experiencing bad symptoms. But it's really up to you what you feel comfortable with.

 

In my opinion you have two options if you choose to not taper linear:

1) You can start at the higher end of the percentage rate and see how things go (which does carry a higher risk of crashing and holding)

2) You can start with a more average approach of around 8% and if all goes well, then you steadily increase your % to what is tolerable for you.

 

When we've had a good run with a fast taper and we hit a bit of a bump, the initial reaction is to just push through. Having experienced acute wd though, I do not wish that on anyone, and there are no guarantees that any person will bounce back quickly and return to their previous state just by reinstating or updosing. The goal now is to avoid this and provide your body with consistency. Too much continuous fluctuation could possibly cause a lot of damage.

 

You do seem to have very reasonable expectations about your ongoing taper though. As mentioned before based on forum experience, your current taper plan seems to be quite aggresive, so let us know whether or not you want to adjust your taper rate on your original post and you want us to take a look at it again.

 

I was able to track down the full article you were referring to (or it states it is the full article, whether it actually is I'm not sure because it lacks a lot of information). I cannot post it here as there are copyright issues.

 

I appreciate researchers looking into this and attempting studies. When reading research studies we have to examine the reliability and validity of the study.

 

This study discloses very little information which makes it extremely difficult to ascertain whether it meets reliability and internal and external validity requirements.

 

First the sampling is problematic as it's very small and cannot be generalized. Another problem is the definition of symptoms and how they identify "mild" wd symptoms. There's no definition of what constitutes mild. Their interpretation of mild and our interpretation may be quite different.

 

Secondly the way they did the rating of symptoms seem problematic. They did not ask patients to rate their own wd symptoms on a scale, rather the severity was rated according to the judgement of an investigator. I find it difficult to comprehend how an investigator can objectively assess the severity of wd symptoms such as anxiety, nausea, nightmares, weakness, headaches etc. across a range of patients. I also question how they accounted for patients having different thresholds when it came to wd symptoms.

 

They further state that "multiple episodes of the same complaint were counted only once per period, although rated at the greatest level of severity". This means they did not examine the wd experience as a holistic experience the way we experience it and disregarded symptoms once recorded at it's severest level after each period.

 

Personally I think this study is probably not the best example and approach to wd. But that's just my opinion based on the info available.

 

I was able to track down the full article you were referring to (or it states it is the full article, whether it actually is I'm not sure because it lacks a lot of information). I cannot post it here as there are copyright issues.

 

I appreciate researchers looking into this and attempting studies. When reading research studies we have to examine the reliability and validity of the study.

 

This study discloses very little information which makes it extremely difficult to ascertain whether it meets reliability and internal and external validity requirements.

 

First the sampling is problematic as it's very small and cannot be generalized. Another problem is the definition of symptoms and how they identify "mild" wd symptoms. There's no definition of what constitutes mild. Their interpretation of mild and our interpretation may be quite different.

 

Secondly the way they did the rating of symptoms seem problematic. They did not ask patients to rate their own wd symptoms on a scale, rather the severity was rated according to the judgement of an investigator. I find it difficult to comprehend how an investigator can objectively assess the severity of wd symptoms such as anxiety, nausea, nightmares, weakness, headaches etc. across a range of patients. I also question how they accounted for patients having different thresholds when it came to wd symptoms.

 

They further state that "multiple episodes of the same complaint were counted only once per period, although rated at the greatest level of severity". This means they did not examine the wd experience as a holistic experience the way we experience it and disregarded symptoms once recorded at it's severest level after each period.

 

Personally I think this study is probably not the best example and approach to wd. But that's just my opinion based on the info available.

 

I share Jelly Baby's well-considered and well-articulated concerns about this study.

 

I also just want to point out that I completely disagree with the "mostly mild" classification of symptom including anxiety, shaking/trembling/tremor, nausea/vomiting, insomnia/nightmares, excessive sweating, tachycardia/palpitations, headache, weakness, and muscle aches.

 

I would be very hesitant to use this information to dictate a tapering approach; it reminds me of the kind of rapid tapers done at detox clinics, but clearly tailored for outpatient doctor-led tapering. My original prescribing doctor told me to taper off in 2-weeks, so while this study explores a far gentler route to the one I was offered, it is still a far cry faster than what has be needed in my actual tapering experience.

 

Edgee, I celebrate that you've made it this far in your taper and at such a rapid rate!

I hope your tapering ease continues. 

 

Personally I think this study is probably not the best example and approach to wd. But that's just my opinion based on the info available.

 

Jelly Belly, thank you for your reply.  I'm just reporting that I had a favorable experience when I followed the Nardi study's method for tapering Clonazepam ("we recommend reducing the dosage of clonazepam after intermediate-term use by 0.25 mg/wk").  I recommend that the curious read the full Nardi paper on sci-hub and make up their own mind about the study:

 

https://sci-hub.do/10.1097/JCP.0b013e3181dcb2f3

 

As you know I reduced from 2.5 mg to 1.0mg over 6 weeks and only experienced symptoms at the very end.  It is not clear to me whether my symptoms are due to WD or an underlying anxiety disorder.

 

 

 

 

Wishing you all the best with your taper.

 

Let us know it's going and how you're doing!

 

I was able to track down the full article you were referring to (or it states it is the full article, whether it actually is I'm not sure because it lacks a lot of information). I cannot post it here as there are copyright issues.

 

I appreciate researchers looking into this and attempting studies. When reading research studies we have to examine the reliability and validity of the study.

 

This study discloses very little information which makes it extremely difficult to ascertain whether it meets reliability and internal and external validity requirements.

 

First the sampling is problematic as it's very small and cannot be generalized. Another problem is the definition of symptoms and how they identify "mild" wd symptoms. There's no definition of what constitutes mild. Their interpretation of mild and our interpretation may be quite different.

 

Secondly the way they did the rating of symptoms seem problematic. They did not ask patients to rate their own wd symptoms on a scale, rather the severity was rated according to the judgement of an investigator. I find it difficult to comprehend how an investigator can objectively assess the severity of wd symptoms such as anxiety, nausea, nightmares, weakness, headaches etc. across a range of patients. I also question how they accounted for patients having different thresholds when it came to wd symptoms.

 

They further state that "multiple episodes of the same complaint were counted only once per period, although rated at the greatest level of severity". This means they did not examine the wd experience as a holistic experience the way we experience it and disregarded symptoms once recorded at it's severest level after each period.

 

Personally I think this study is probably not the best example and approach to wd. But that's just my opinion based on the info available.

 

I share Jelly Baby's well-considered and well-articulated concerns about this study.

 

This hardly comes as a surprise given your advocacy for extremely slow, exponential decline tapers.  I am agnostic on the "slownsteady" approach.  What matters to me is whether a taper works and how fast it is.  I don't want to be tapering for years on end.  I don't think there's anything wrong with your advocating for what you believe in, so long as you are clear with your audience that you are engaged in advocacy, and don't misrepresent your advocacy as dispassionate scientific reasoning. 

 

I experience your critique as factually wrong in places and a caricature of what the authors said in others.

 

 

I also just want to point out that I completely disagree with the "mostly mild" classification of symptom including anxiety, shaking/trembling/tremor, nausea/vomiting, insomnia/nightmares, excessive sweating, tachycardia/palpitations, headache, weakness, and muscle aches. Only ~50% of the patients were able to cease the medication on this timetable, and ~26% of patients required almost twice as long. What about the remaining ~25% of patients?

 

Your success stats are completely wrong.  The researchers did far better by their patients than you so confidently state.  See p. 292 of the original study, "Results":

 

https://sci-hub.do/10.1097/JCP.0b013e3181dcb2f3

 

I don't like those symptoms or those odds. Thus I would be very hesitant to use this information to dictate a tapering approach; it reminds me of the kind of rapid tapers done at detox clinics, but clearly tailored for outpatient doctor-led tapering. My original prescribing doctor told me to taper off in 2-weeks, so while this study explores a far gentler route to the one I was offered, it is still a far cry faster than what has be needed in my actual tapering experience.

 

 

1. You're wrong about the odds so you're conclusion is based on a faulty premise.  This kind of sloppiness with the facts is not what I expect in scientific discourse.  2.  IMO, you are engaging in hyperbole or caricature of the study's results to compare them to a detox clinic.  The study taper was 4 months, plus another 3 if the patient needed it.  Stop putting your thumb on the scale if you want me to take you seriously.

 

Edgee, I celebrate that you've made it this far in your taper and at such a rapid rate!

I hope your tapering ease continues. 

 

Thank you for the kind words.  My goal is somewhat more complicated than "tapering success".  I think it is possible that I will be on benzos for life.  If that is the case, I want to find the absolute minimum dose I can live with. 

Thanks for your feedback Edgee! It appears I misread the abstract which says...

 

In total, 51 (68.9%) of the patients were free of the medication after the 4 months of tapering according to the protocol, and 19 (26.0%) of the patients needed another 3 months to be free of medication.

 

Edgee, I celebrate that you've made it this far in your taper and at such a rapid rate!

I hope your tapering ease continues. 

 

I also hope you find more of the "scientific discourse" you are looking for!

Many buddies make light work. 

Thanks for your feedback Edgee! It appears I misread the abstract which says...

 

 

slownsteady, you're too kind.  I wouldn't call it feedback, but rather criticism of your post. IMO, this violates the mission statement of benzobuddies which states in pertinent part:

 

BenzoBuddies: an inclusive, nonjudgmental mutual-support environment for those who wish to withdraw from benzodiazepines.

Members of the BenzoBuddies community are encouraged to exchange ideas, information and support during the process of withdrawal and recovery.

 

Let me see if I can reformulate my criticism of your post in a supportive, nonjudgmental way.  You write beautifully.  I think, however, that you do yourself a disservice when you voice strong opinions that are not grounded in accurate facts, e.g., when you disparaged the results of the Nardi study ("I don't like those symptoms or those odds.").  How can people trust your other work e.g., on DMTs and Klonopin if they suspect that you sometimes play fast and loose with the facts?  Therefore, I suggest you either 1. read the entire scientific study before commenting on its results or 2. refrain from commenting on scientific work that you have not carefully reviewed.

 

Finally, I wish you would be a bit more open to other approaches to tapering besides a liquid DMT.  I suspect that a "one size fits all" approach simply would not meet the needs of many of the people who are trying to get off benzodiazepenes (too hard to understand, slow etc.).

 

I also hope you find more of the "scientific discourse" you are looking for!

 

I'm not looking for scientific discourse on benzobuddies.  But regarding the technical/scientific aspects of benzodiazepine withdrawal, I hope people on BB will take the time and make the effort to ground their opinions in accurate facts.

Your opinions are welcome here Edgee. 

Your opinions are welcome here Edgee. 

 

slownsteady, thank you for your reply.  Here's one more opinion for your consideration, this one not from me:

 

"Everyone is entitled to his own opinion, but not his own facts." --Sen. Daniel Patrick Moynihan

 

If I've failed to ground my own opinions in accurate fact, please let me know.

 

 

But regarding the technical/scientific aspects of benzodiazepine withdrawal, I hope people on BB will take the time and make the effort to ground their opinions in accurate facts.

 

Excellent point, Edgee.  I agree. May I give an example?  I’d like to encourage all interested readers to carefully review the study being used to derive a “recipe” for a homebrew clonazepam liquid. See citation and link below.

 

First, note that the purpose of the study was to generate experimental data to train a mathematical model to predict drug solubility for use in the pharmaceutical industry.  The purpose of the study was not to develop and test liquid drug formulations that would be safe and effective for human use.

 

Second, the researchers used different ingredients and different procedures than those used by homebrew “kitchen compounders”. In terms of ingredients, the researchers used the pure active drug substance (not regular tablets) as the drug source, 99.9% pure ethanol (not off-the-shelf vodka or Everclear), and double-distilled water (not tap water). 

 

In terms of procedures, the researchers added excess amounts of the active drug substance to water/ethanol mixtures ranging from 0% ethanol (all water) to 100% ethanol.  They then agitated these drug/water/ethanol mixtures in an incubator at an elevated temperature for 48+ hours to achieve saturated solutions. Next, they used micron filters to separate the solid and liquid phases of the saturated solutions and diluted the liquid phases with methanol. Lastly, they analyzed the drug content in the diluted liquids to determine solubility.

 

The above facts suggest caution is warranted when using the experimental solubilities from this study to inform “recipes” for homebrew clonazepam liquids. 

 

It is also important to note that the solubility of a drug is just one of many factors that require consideration during liquid drug formulation.  For example, another important consideration is the stability of the liquid — chemical, physical, microbiological, therapeutic, and toxicological.

 

Citation:

 

Shayanfar, Ali; Fakhree, Mohammad Amin Abolghassemi; Acree, William E. (William Eugene) & Jouyban, Abolghasem. (2008). Solubility of Lamotrigine, Diazepam, and Clonazepam in Ethanol + Water Mixtures at 298.15 K. Accessed online at: https://digital.library.unt.edu/ark:/67531/metadc674044/)

 

Edited for clarity and to correct copy/paste error.

 

In terms of procedures, the researchers added excess amounts of the active drug substance to water/ethanol mixtures ranging from 0% ethanol (all water) to 100% ethanol.  They then agitated these drug/water/ethanol mixtures in an incubator at an elevated temperature for 48+ hours to achieve supersaturated solutions. Next, they used micron filters to separate the solid and liquid phases of the supersaturated solutions, diluted the liquid phases with methanol, and then analyzed the drug content in the diluted liquids to determine the degree of solubility.

 

The above facts suggest caution is warranted when using the experimental solubilities from this study to inform “recipes” for homebrew clonazepam liquids. 

 

Wow.  So pouring a couple of ml of Everclear on top of my Klonopin pills may not result in a solution of known dilution?  I think your post should be incorporated into slownsteady's recipe as a disclaimer:  THIS MAY NOT WORK.  Ugh.  I guess I'll stick with compounding pharmacies then if I ever need liquid Klonopin.

The above facts suggest caution is warranted when using the experimental solubilities from this study to inform “recipes” for homebrew clonazepam liquids. 

 

It is also important to note that the solubility of a drug is just one of many factors that require consideration during liquid drug formulation.  For example, another important consideration is the stability of the liquid — chemical, physical, microbiological, therapeutic, and toxicological.

 

Libertas, what would it take to validate slownsteady's recipe for liquid Klonopin?  What evidence would you need to see to say "yes, this works"?

Hi Edgee,

 

I've not been following the recipes promoted or discussed by any member of late - but did so (to a limited degree) about 18 months ago. If members are going to discuss home titration, this necessarily involves discussion of ratios and some basic maths - and that's OK. But as you imply, such discussion should carry caveats regarding the limitations of any such methods, the known risks, and the unknowns. Although I have not read through slownsteady's 'recipe', I expect that it will suffer from similar problems associated with all such 'home brew' methods I've seen discussed at BB and elsewhere.

 

What I expect we will do is add further advice for members about home titration of benzodiazepines. Apart from the limitations already outlined in other posts above, there is also a general push for unreasonable exactitudes with home titration. Very often (I am not saying that this occurs in slownsteady's discussions - I've not read them) we see proponents push for 'solutions' to an accuracy in the range of 0.1 to 1.0 %. But, since tablet doses typically vary from nominal (stated) doses by at least a few percent, and interdose withdrawal results in blood levels dropping by at least a few percent (even for a long half-life benzodiazepine taken twice per day), what is the point of aiming for exactitudes of (at least) an order of magnitude greater than what is achievable even in the best of circumstances?

 

But these are two separate problems: one of unrealistic expectations; and the other, where even basic expectations are unsatisfied. The first problem where there may be unnecessary and unrealistic goals: aims of 0.1 to 1.0% reductions in dose are swamped by much larger and unavoidable variables. The second is potentially much more dangerous: where the resultant 'solution' does not even deliver anything like a reliable dose and/or is prone to spoiling.

 

We've had occasion to tackle these problems several times over the years at BB. The last occasion was about 18 months ago. We posted some advice for members at the time (and we will add more soon):

 

http://www.benzobuddies.org/forum/index.php?topic=231363.0

 

http://www.benzobuddies.org/forum/index.php?topic=231828.0

 

You might also read this thread, detailing problems, the origins of which lie firmly outside of BB:

 

http://www.benzobuddies.org/forum/index.php?topic=231882.0

 

It is not easy deciding upon where to draw sensible lines for a discussion forum which also aims to provide support. But the information (above) provided by Libertas will form the core part of another planned overhaul of information we provide to members about titration.

In terms of procedures, the researchers added excess amounts of the active drug substance to water/ethanol mixtures ranging from 0% ethanol (all water) to 100% ethanol.  They then agitated these drug/water/ethanol mixtures in an incubator at an elevated temperature for 48+ hours to achieve supersaturated solutions. Next, they used micron filters to separate the solid and liquid phases of the supersaturated solutions, diluted the liquid phases with methanol, and then analyzed the drug content in the diluted liquids to determine the degree of solubility.

 

This is an interesting interpretation of the study you shared with me Libertas.

 

True, the researchers used excess active drug substance, and agitated them for 48 hours in a temperature stable environment. Your described "elevated temperature" is 298.15 K which is 77 degrees Fahrenheit; not exactly elevated from a human-habitation point of view.

 

Nowhere in the study can I find the phrase supersaturated, though you repeatedly describe the results as this. Why would they neglect to mention their results are supersaturated, when the introduction indicates the research goal is to explore ethanol + water solutions specifically for "the preparation of liquid drug formulation stages in the pharmaceutical industry."? To my understanding a supersaturated solution would be highly unstable, and unsuitable for liquid drug formulation.

 

My pharmacist took a look at this study and agreed that the information presented in Table 4. was sufficient evidence to formulate 0.125mg/ml clonazepam solution in 30% ethanol by volume; she suggested that even more medicine could be compounded in the same ethanol ratio, as the research data appears to indicate. That being said, I like my wide margins of error.

 

I agree with any and all concerns that this study does not prove anything about a home made liquid medicine, nor even a pharmacy compounded formula involving ethanol and water. However, there is seemingly a very real present need for individuals to taper their benzo tablets, often times without the assistance of a pharmacist or even a prescribing doctor. Even myself, fortunate enough to have both, was unable to tolerate or utilize two formulations that were pharmacy compounded (one proprietary and stability tested, and the other in pure MCT oil). "My recipe" which is a part of my personal tapering notes, is the result of necessity and circumstance, as are so many other diverse decisions made by taperers across the forum.

 

I am all for giving every warning and caution and indication that without assaying the results of each and every individual shaved pill, and each and every individual liquid dissolution of tablets or "active drug substance", there is no guarantee the medicine expected is being delivered. As Colin suggested, various margins of error exist throughout medicine and life, which in my mind, become insignificant past a certain point.

 

In my opinon, if a taperer can safely and comfortably reduce with the method in use, I think it's a viable method for them. Buddies looking to start tapering will no doubt have to do trials to find what their unique physiology and circumstances can tolerate, and offering a variety of tried and often successful methods for them to begin exploring is what I think BB does SO well. Conversely, offering a one-size-fits-all rule book, or a warning against trying anything at home, doesn't seem like it's going to go very far in helping our current crisis.

 

Thanks for your consideration, and please accept my invitation to chime in on any thread I'm on with additional warnings or considerations that you deem necessary; I have no personal agenda in getting anyone to taper a specific way. I specifically give suggestions that I hope will minimize risks, help the taperer to learn more about their body in a slow and gentle way, and hopefully reach their tapering goals.

 

Thanks Colin for the links which I remember seeing before, but which would save me a lot of typing if I could grab them while trying to help taperers put titrating in perspective. We swim in turbulent waters! Anything that you can do to preserve the experiential wisdom of the forum, while giving perspective to the risks we take in our methods, I certainly welcome.

 

Then again: no risks, no rewards. 

In terms of procedures, the researchers added excess amounts of the active drug substance to water/ethanol mixtures ranging from 0% ethanol (all water) to 100% ethanol.  They then agitated these drug/water/ethanol mixtures in an incubator at an elevated temperature for 48+ hours to achieve supersaturated solutions. Next, they used micron filters to separate the solid and liquid phases of the supersaturated solutions, diluted the liquid phases with methanol, and then analyzed the drug content in the diluted liquids to determine the degree of solubility.

 

This is an interesting interpretation of the study you shared with me Libertas.

 

True, the researchers used excess active drug substance, and agitated them for 48 hours in a temperature stable environment. Your described "elevated temperature" is 298.15 K which is 77 degrees Fahrenheit; not exactly elevated from a human-habitation point of view.

 

Nowhere in the study can I find the phrase supersaturated, though you repeatedly describe the results as this. Why would they neglect to mention their results are supersaturated, when the introduction indicates the research goal is to explore ethanol + water solutions specifically for "the preparation of liquid drug formulation stages in the pharmaceutical industry."? To my understanding a supersaturated solution would be highly unstable, and unsuitable for liquid drug formulation.

 

This is true, but I think Libertas' point--that you have departed significantly from the researchers' protocol for putting Klonopin into solution--stands.  For example, you don't recommend 48 hours of agitation in your homebrew recipe.  For another you are not using pure drug substance in your recipe, but Klonopin pills in which the excipient to Klonopin ratio by weight is 150:1.

 

 

My pharmacist took a look at this study and agreed that the information presented in Table 4. was sufficient evidence to formulate 0.125mg/ml clonazepam solution in 30% ethanol by volume; she suggested that even more medicine could be compounded in the same ethanol ratio, as the research data appears to indicate. That being said, I like my wide margins of error.

 

Did your pharmacist use pure drug substance or pills in preparing her compound?  If the former, then IMO this is not evidence in favor of your homebrew recipe.

 

 

I agree with any and all concerns that this study does not prove anything about a home made liquid medicine, nor even a pharmacy compounded formula involving ethanol and water.

 

Right.  Specifically, we don't know:

 

However, if you are using a "home brew' liquid made with regular tablets, it is unknown if you are getting an accurate dose. Why? To our knowledge, none of the home brew liquids have been tested for homogeneity (we do not know if they are true solutions), potency, or stability over time. We also do not know the pharmacokinetic properties of home brew liquids (i.e. absorption, distribution, metabolism, elimination).

 

What evidence do we have that your recipe is safe and effective?  Well, we have a tiny bit of anecdotal evidence in your favorable experience with your recipe, so it's probably safe.  Has anyone else reported good results using your recipe? 

 

If I had to speculate, I would say that your recipe at worst provides people with less than the stated dose of Klonopin.  You've arranged things so that the bulk of the cutting is done will pills and at most 1/8 mg of Klonopin is in liquid form.  If worst case your recipe is inert, you are doing a cut and hold taper in 1/8 mg steps--which doesn't sound dangerous to me. 

 

 

 

 

Hello Edgee. Thank you for correctly and succinctly identifying the main point I wanted to make about the study — that is, the researchers’ protocol for creating solutions of benzo/ethanol/water to derive experimental solubilities differs significantly from that used by “kitchen compounders” making homebrew liquids.

 

FYI - In re-reading my original post, I discovered I made a copy/paste error (now corrected) that resulted in the word “supersaturated” being substituted for “saturated.”  Fortunately, this inadvertent substitution was not relevant to the point I was making.