Considering Liquid DMT Titration of Klonopin

Hey all. Hope everyone is doing as well as they can be. I am considering this method as my dry micro cuts are getting larger as I get lower in dose.

 

I am currently at 0.135 mg klonopin. I do not want to take the alcohol approach and am considering the whole milk approach.

 

Still trying to wrap my head around the calculations. Would really appreciate some feedback or guidance on how much liquid to use, how many pills, how much to reduce each day, etc. I tried the online benzo always data calculator but am not getting good information.

 

Thanks,

Seekingtoheal

Perhaps of interest ...

 

J Stone (clonazepam)

http://www.benzobuddies.org/forum/index.php?topic=232589.msg2985248#msg2985248

 

Crazy Canuck - Benzo Detox (clonazepam)

Thanks. One concern I have is you have to discard unused every day.

I wrote this instructional to help people use Jim Hawk's generator:

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

 

It can be used with the milk suspension method, if that's your fancy. And yes, the milk suspension is sometimes done as a daily discard, but it doesn't have to be. I believe you could make a milk suspension containing a few days worth of medicine and keep the remainder in the fridge between doses; this would consist of making a new batch every few days when the old batch is finished. No medicine would be discarded with this approach.

 

I'd be happy to help you work out a milk suspension batch size based on your tablets and doses. 

Thanks. Will keep this in mind if I pursue.

 

Appreciate the feedback.

I wrote this instructional to help people use Jim Hawk's generator:

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

 

It can be used with the milk suspension method, if that's your fancy. And yes, the milk suspension is sometimes done as a daily discard, but it doesn't have to be. I believe you could make a milk suspension containing a few days worth of medicine and keep the remainder in the fridge between doses; this would consist of making a new batch every few days when the old batch is finished. No medicine would be discarded with this approach.

 

I'd be happy to help you work out a milk suspension batch size based on your tablets and doses. 

 

Very much considering homogenized milk liquid taper now. At 0.121 mg and looking to start at trying to drop 0.001 mg every day. Trying to understand the process, math, and what I need to buy to use. I also would rather not waste any of the medication as I am not sure I can get a refill. I have 90 0.5 tablets left so supply should be ok.

 

Thanks, Seeking

Also considering a propylene glycol / water combination as well. Not sure which one milk or PG|water would be better for say a 10 day run.

Just offhandedly, I would not trust a milk batch to last 10 days. Maybe the medicine would be fine, but there's no strong preservatives in there and it's milk! Someone else who buys and drinks pasteurized and homogenized full-fat milk could maybe speak to this with more confidence; I'd just be concerned.

 

Maybe milk plus some preservative would last 10 days. Maybe a little alcohol? But then we're on the way to an ethanol and water mixture...

 

Speaking of ethanol, while purported to be 3x more toxic than PG (https://en.wikipedia.org/wiki/Propylene_glycol), it is more effective at dissolving clonazepam. However it appears to me that PG has a superior solubility-to-toxicity ratio in formulas with 0-30% in solution and 70-100% in solution. By my math, ethanol still out-performs PG by more than 3x in solutions with 40-60% in solution.

 

Clonazepam	
% PG	mg/ml
0%	0.032
10%	0.035
20%	0.057
30%	0.088
40%	0.183
50%	0.309
60%	0.865
70%	1.481
80%	2.810
90%	3.703
100%	5.853

https://sci-hub.se/10.1021/je800931z

 

Clonazepam	
% Ethanol mg/ml
0%	0.032
10%	0.041
20%	0.079
30%	0.199
40%	0.600
50%	1.427
60%	2.639
70%	4.218
80%	5.645
90%	6.178
100%	5.111

https://sci-hub.se/10.1021/je8007827

 

Since you're at low doses, I'm thinking you'll be wanting a 0.0625mg/ml solution or lower. This might require something like a 30% PG to water solution, which has a favorable solubility to toxicity ratio when compared to ethanol and was shown to dissolve a maximum saturation of 0.088mg/ml pure clonazepam after 72 hours of constant agitation in a temperature stable incubator. This is clearly not the same as trying to dissolve tablets at home, but this is the best data I know of for making some guesses and comparisons.

 

Also, FYI, some people are allergic to PG.

Because of its potential for allergic reactions and frequent use across a variety of topical and systemic products, propylene glycol was named the American Contact Dermatitis Society's Allergen of the Year for 2018.

(https://en.wikipedia.org/wiki/Propylene_glycol)

 

Just some details I could dig up for your consideration. Math not guaranteed.

I hope this helps. 

"I'm thinking you'll be wanting a 0.0625mg/ml solution or lower." 

 

How would I do that with whole milk suspension for .120 mg and do a plan to drop 0.001 mg a day for 120 days? Since I take at night I want to use the least amount of milk (no mid morning bathroom)

 

Still trying to wrap my head around how to do this. I assume I need a 50 ml or 100 ml graduated cylinder, and I assume a syringe that can do 0.1 ml increments.

 

Thanks.

 

 

 

 

"I'm thinking you'll be wanting a 0.0625mg/ml solution or lower." 

 

How would I do that with whole milk suspension for .120 mg and do a plan to drop 0.001 mg a day for 120 days? Since I take at night I want to use the least amount of milk (no mid morning bathroom)

 

Still trying to wrap my head around how to do this. I assume I need a 50 ml or 100 ml graduated cylinder, and I assume a syringe that can do 0.1 ml increments.

 

Thanks.

 

I was discussing your options for using a solvent in that sentence you quoted.

 

Some people around the forum say that some benzos are lipid soluble, but I've never seen research data that supports that claim with any details about this kind of solubility. I consider the milk method to be a homogenized-fat based suspension, but I welcome any verifiable information that says otherwise. I've had my clonazepam powder sit for months in MCT oil which is pure fat, and if it ever dissolved it was such a small amount that I could not tell; the mixture remained primarily a suspension so at least for clonazepam I doubt that lipid solubility is a viable option.

 

For the milk method with K, I think it's important to rely on the variables that support a water suspension, and one of these is using a relatively large volume of the suspension vehicle. I've never done a milk suspension, but there are videos on YouTube with examples.

 

Since you've mentioned wanting to produce multiple days worth of liquid, I'd be inclined to use 0.005mg/ml with milk at your doses. A dose of 0.120mg would be 24ml, and each day reducing by 0.001mg would be a 0.2ml reduction. One way to do this would be to use a 10ml oral syringe with 0.2ml gradations (4 lines between each 1ml mark); it would take three pulls to get the 24ml to start, two 10ml pulls and one 4ml pull.

 

Since 0.005mg/ml requires ~24ml/day at this point, a batch size might be 100ml containing 1x 0.5mg tablet. One way I might produce this batch would be with a 100ml graduated cylinder and a glass stir rod; adding the tablet first to the cylinder (to get an accurate final volume), and then adding milk to where the meniscus reads at the 100ml line. Wait 10-15 minutes for tablet deconstruction, stir vigorously, and then transfer to a small sealed bottle (ideally a medicine bottle with an oral syringe adapter). I would shake this bottle vigorously immediately before drawing a dose. I would store this bottle in the refrigerator between uses. I would probably discard any remaining after 5 days or so.

 

Again I have not used the milk method. I think some people do it with MUCH larger quantities of milk, and perhaps that is easier to measure with less accurate tools and more stable in suspension. I was thinking of a smaller batch to save on syringe volumes and since graduated cylinders that I've seen max at around 100ml. But some people use the metric or cup measurements on the side of a Mason jar to measure 240-300ml and beyond and this could be all the accuracy needed. The syringe draws would be much larger with a larger volume but this could improve the accuracy of measurements with cheaper tools. 0.001mg adjustments of a 0.001mg/ml milk suspension (1x 0.5mg in 500ml total volume with milk) would be in the 1ml range, and the starting daily dose would be 120ml (1/2 cup).

 

Just some ideas of mine to consider. I hope this helps. 

Yes thank you for your time and detailed insight.

slow a couple of more clarifications. Say I want to produce a 3 day batch. (thinking of shelf life so reduced to 3 days). Assuming  0.005 mg/ml concentration then .120 mg is 24 ml. Noted reducing by 0.001 mg daily would be a 0.2 ml reduction each day for a 120 day taper period. So for a 3 day batch I need at least (24 ml x 3 days) = 72 ml to meet that 3 day requirement. I think I got all that.

 

By making a 0.5 mg/100 ml batch that gives me the 0.005 mg/ml concentration and enough ml to cover 3 days (3 day need is 72 ml batch is 100 ml)

 

If I produced that batch amount for 3 days use then would my taper approach be below:

 

Day 1: (.120mg) = take 24 ml

Day 2 (0.001 mg drop) = take 23.8 ml

day 3 (0.001 mg drop) = take 23.6 ml

Discard, make new batch and repeat with 0.2 ml decrements.

 

thanks seeking

 

 

seekingtoheal:  Tip of the hat for devising a way to make and use a 3-day batch of clonazepam/milk homebrew. Your reasoning and calculations look spot on to me.  My only suggestion is to be cautious about reducing your dose by a fixed amount — this may work for a while but you may reach a point where you need to adjust the amount.  As the saying goes, “Let your symptoms be your guide.”

 

Fyi We have many members who have used milk to taper clonazepam over the years.  Current members GumbyGirl and Intend to be off come to mind.

 

slownsteady:  Per your request for information about the lipophilicity of benzodiazepines:

Benzodiazepines are highly protein bound (70-99%) but rapidly distribute to CNS. Benzodiazepines cross the blood brain barrier (BBB) by passive diffusion, and thus, the rate of CNS distribution correlates with lipophilicity.

 

Since all benzodiazepines are relatively lipophilic, their degree of lipophilicity influences the duration of clinical effect of the medication. Diazepam and midazolam are the most lipophilic, and have the fastest onset of action.


 

Source:

Introduction to Benzodiazepines - PsychDB

https://www.psychdb.com/meds/benzos/home

 

My understanding is that lipophilicity is represented, in part, by the descriptor logP.  Per PubChem, experimental logPs are: midazolam 4.33, diazepam 2.82, clonazepam 2.41, lorazepam 2.39, alprazolam 2.12.

 

See also: Griffin, C. E. et al. (2013). Benzodiazepine pharmacology and central nervous system–mediated effects. Ochsner Journal, 13(2), 214-223.  Available online at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3684331/

Libertas thanks to you and slow. I figured 3 days was a good benchmark for retention instead of 5 days. I also though about using propylene glycol/water instead of milk (want to stay away from any alcohol based) but am unsure if milk or PG/water is one better than the other.

It sounds like you've got the details worked out seekingtoheal!

I think a 3-day batch sounds good to start.

---

 

Libertas, you must have a good milliner; seems you're always wearing a hat!

Thank you for this info about benzo lipid solubility.

 

Per the journal article you linked to...

Because clonazepam displays low lipid solubility, it is less likely to cause anterograde amnesia compared to the other high-potency BZDs. For example, clonazepam is half as lipid soluble as alprazolam, so patients' amnesic side effects are reduced.

(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3684331/)

 

"Half as lipid soluble", yet the logP given for clonazepam is 2.41 while alprazolam is 2.12. This has me confused. I don't know how to interpret logP values to make any comparison between the values you've shared. I'd be curious if you know mg/ml values for lipid solubility of clonazepam; I get dizzy whenever log-anything shows up on a research report. 

 

I can't imagine milk having more lipids than the pure MCT oil that I found was unable to dissolve 0.125mg/ml of pure clonazepam but I digress; I always suggest treating liquids from tablets as suspensions regardless of ingredients. Better safe than sorry IMO.

This is prob old news but I found a compounding recipe for K using Ora plus (can purchase on Amazon). It has a 60 day expiration.

 

https://www.nationwidechildrens.org/-/media/nch/specialties/pharmacy/compounding-formulas/clonazepam-oral.ashx?la=en&hash=BBD3E4A5E334418EF12A25A8E09E6BF8

 

 

This is prob old news but I found a compounding recipe for K using Ora plus (can purchase on Amazon). It has a 60 day expiration.

 

https://www.nationwidechildrens.org/-/media/nch/specialties/pharmacy/compounding-formulas/clonazepam-oral.ashx?la=en&hash=BBD3E4A5E334418EF12A25A8E09E6BF8

 

Thanks

Hey all going to summarize my approach and please poke holes in it as needed. As noted this is my "planned" approach and will tweak as needed on how I am managing.

 

- Concentration - 0.005 mg / 1 ml

- My current dosage of klonopin is 0.120 mg so my starting ml dosage will be 0.120 mg / 0.005 mg = 24. 24 x 1 ml = 24 ml

- Batch production target: 1 0.5 mg tablet with 100 ml of whole milk (8%fat) to make 3 (72 ml) or 4 days (96ml) supply

- Initial plan is to target reducing 0.001 mg a day [0.2 ml]

 

Approach:

 

- Mix 0.5 mg table into 100 ml whole milk in a suitable glass jar.

- Put in refrigerator at least 24 hours before plan to use for good absorption into a suspension

 

Usage

 

- shake up suspension in glass jar to ensure dispersion

- take a 10 ml syringe with 0.2 ml increments

- work out air bubbles

 

- Day 1 - extract 10 ml consume, extract 10 ml consume, extract 4 ml consume = 24 ml

- Day 2 - extract 10 ml consume, extract 10 ml consume, extract 3.8 ml consume = 23.8 ml

- Day 3 - extract 10 ml consume, extract 10 ml consume, extract 3.6 ml consume = 23.6 ml

- Day 4 - extract 10 ml consume, extract 10 ml consume, extract 3.4 ml consume = 23.4 ml

 

Repeat

 

thanks, seeking.

 

 

 

Hello again, seekingtoheal.

 

I’m glad you have decided to give milk a try.  Compared to propylene glycol/water, milk has been used to taper clonazepam by more members for more years. (I personally have encountered only a handful of members who have tried using PG/water with clonazepam. I also have concerns about the benzo:PG:water ratio you may have read about when it is used with clonazepam tablets.)

 

Your plan for the first week of your taper looks solid to me.

 

Do you have a sense of what your optimal taper rate is?  How about your withdrawal pattern? If not, you might want to consider adding strategic holds to your taper plan.  For example, on Day 7, you will consume 22.8mL of your homebrew.  This represents a 5% reduction in dose over 7 days.  To evaluate if you can tolerate that taper rate, you could hold at that dose for at least 3 days to give your body time to process the reductions made and for any withdrawal symptoms to emerge (see explanation below).  If you experience withdrawal symptoms, you could continue holding until they stabilize. (Stabilize does not mean no symptoms but rather symptoms are not getting worse and are tolerable enough for you to make the next reduction.)

 

I have no personal experience with homebrew milk, but I have read that full-fat milk may bubble if it is shaken too vigorously.  The Withdrawal Project has tips on how to deal with this (as well as other tips for using syringes and liquids) at:

https://withdrawal.theinnercompass.org/taper/using-syringes

 

Explanation:

I’ve read that in most clinical situations the attainment of a steady-state plasma concentration of a drug can be assumed after 3-5 half-lives. The half-life of clonazepam is relatively long (I’ve seen estimates ranging from 18 to 50 hours). So, depending on how your body processes the drug, steady state could be attained in as few as 54 hours to as many as 225 hours.

 

PS One of our members who earned an MD as well as a Ph.D. in pharmacology, explained the theory behind using milk as follows: Lipophilic drug molecules have an affinity for the fat molecules in milk. In non-homogenized milk, fat molecules are not evenly distributed; they rise to the top to form a layer of cream. The process of homogenization breaks the fat molecules down to a smaller size so this separation does not occur; the fat molecules (and hence the affiliated “lipid liking” drug molecules) are suspended throughout the milk.

Hello again, seekingtoheal.

 

Do you have a sense of what your optimal taper rate is?  How about your withdrawal pattern? If not, you might want to consider adding strategic holds to your taper plan.  For example, on Day 7, you will consume 22.8mL of your homebrew.  This represents a 5% reduction in dose over 7 days.  To evaluate if you can tolerate that taper rate, you could hold at that dose for at least 3 days to give your body time to process the reductions made and for any withdrawal symptoms to emerge (see explanation below).  If you experience withdrawal symptoms, you could continue holding until they stabilize. (Stabilize does not mean no symptoms but rather symptoms are not getting worse and are tolerable enough for you to make the next reduction.)

 

 

Does it serve any benefit to crush the klonopin pill with a mortal/pestle before adding to the milk or just drop the pill in the milk? Not sure what the ample time would be to let the pill dissolve in milk.

 

Thanks for the detailed reply Libertas. Not completely sure on what my optimal taper rate is. I was doing ok in the 1-1.5% daily cut range when I was tapering 0.001 g every day or every other day. (When I got to 0.150 mg I had to start doing every 3rd day cuts as the cuts got to be around 2% drop each time). With the dosage I am at now (0.120 mg the 0.001 g cuts represent almost a 2.5% cut each time I do it with a 0.001 g drop). The withdrawal pattern has been perplexing to me. By doing a daily, every other day, every third day DMT I am not sure what I am feeling as related to when I would do a cut. Added to my mix is that I also take 3.5 mg of Remeron and 30-40 mg of melatonin at night coupled with the klonopin to get sleep. Will definitely keep the 3 day hold in mind.

 

thanks,

seeking

 

 

 

Edit: fixed quote

Speaking of ethanol, while purported to be 3x more toxic than PG (https://en.wikipedia.org/wiki/Propylene_glycol), it is more effective at dissolving clonazepam. However it appears to me that PG has a superior solubility-to-toxicity ratio in formulas with 0-30% in solution and 70-100% in solution. By my math, ethanol still out-performs PG by more than 3x in solutions with 40-60% in solution.

 

Should this be something to be concerned about? Is it the toxicity of the alcohol mixed with the clonazepam? As long as you have a solution in the 40 to 60% range, you should be okay? It just seems easier to me than milk to get an accurate amount of clonazepam out of the suspension (and I'd rather avoid PG).

 

Sorry to jump into this conversation, but I'm considering the same type of taper after four months of taking K.

Hello, seekingtoheal.

 

I’m glad you are keeping strategic holds in mind. Per Horowitz and Taylor (2019 - see link below), one of the disadvantages of daily microtapering is that it presents the possibility of cumulative withdrawal effects being superimposed on one another. This makes it difficult to establish which reduction (or set of reductions) is responsible for withdrawal symptoms experienced.

 

Re: your question about crushing your clonazepam tablet before adding milk or just dropping the tablet in the milk ...

 

As a general rule of thumb, smooth powder (i.e. smaller and more evenly sized drug/excipient particles) is preferable to chunky tablet fragments (which contain a combination of the active drug substance and excipients). Using a mortar and pestle is one way to achieve a smooth powder. However, if you go this route, please take appropriate steps to avoid loss of the drug/excipient powder due to surface transfer, etc. (see link below to learn more).

 

Dropping the tablet into the milk avoids drug/excipient loss due to surface transfer but introduces a different challenge. Depending on the manufacturer, some tablets do not disperse (disintegrate) quickly and evenly when milk is added.  For example, member GumbyGirl reported that her Activas clonazepam tablets disintegrated quickly in milk whereas her Teva clonazepam tablets did not.

 

For your consideration ... one possible way to get around this would be to place the tablet in the container you use to prepare your homebrew.  Cover the tablet with a small, measured amount of water to “jump start” the tablet disintegration process (be sure to include the measured amount of liquid in the total calculated volume of the liquid).  If the tablet does not disintegrate into even particles within a minute or two, use a glass stirring rod to break up any remaining chunks.  When you add the milk to the disintegrated tablet/water slurry, be sure to “rinse” the stirring rod with the milk to remove any drug/excipients particles that might be clinging to it.

 

Another possible workaround is to obtain and use the clonazepam Orally Disintegrating Tablets (member Intend to be off uses these). As the name implies, these tablets are designed to disintegrate quickly in saliva. (Let me hasten to add that the actual drug molecules in the ODTs do not dissolve — they enter the body the same way as the drug molecules in regular tablets - via the intestinal tract.)

 

Links:

 

Horowitz and Taylor (2019)

https://www.mentalhealthexcellence.org/tapering-of-ssri-treatment-to-mitigate-withdrawal-symptoms/

 

Using a Mortar and Pestle for Pulverizing Tablets

https://withdrawal.theinnercompass.org/taper/using-mortar-and-pestle-pulverizing-tablets

Thanks Libertas. I would completely agree with Horowitz and Taylor. I have been holding almost 7 days and still dealing with heart palpitations and burning/tingling in hands/feet.

 

I tried taking a half of one of my tablets (teva standard 0.5 mg tablet) and put into a small amount of water. After a few minutes, I let it wait about 10 minutes and about 98% of the pill was dissolved.

 

What I might do to create my batch is to put pill in about 2 ml of water to start the dissolve process and then add 98 ml of whole milk and gently stir, etc.

 

thanks,

seeking

 

Slow/Libertas - I am thinking that instead of doing 100 ml of milk I am going to do 50 ml with 0.5 mg tablet. My big concern is drinking liquid at bedtime will make me more prone to awake to go to the bathroom. Is there any concern with using less volume of milk.

Hi seekingtoheal,

Nothing from Libertas' claims or links suggest to me that that clonazepam from a tablet is going to significantly dissolve in whole milk, so I suggest considering your tablet deconstruction a suspension.

 

Since you're not planning to adjust the viscosity of your suspension vehicle, the two variables that I believe will have the most impact on the stability of the milk mixture are the medication particle size and the volume of liquid. Smaller particles stay suspended longer, and larger volumes seem to hold particles in suspension for longer. So the risk I imagine with a smaller volume of milk is a more unstable suspension.

 

I suggest sticking with your 100ml batch size. Your daily dose of 24ml is equivalent to ~1.3 tablespoons; I don't see any benefit in cutting this down to ~0.65 tablespoons while potentially sacrificing dosing accuracy.

 

Also, I don't think you need 24hrs of soak time to get a suspension of your deconstructed tablets but aside from wasting a day towards milk-spoilage, I don't see this being an issue either.

 

Just my two cents.