Mitigation of benzodiazepine dependence, tolerance, and withdrawal

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Benzodiazepine withdrawal is one of the worst things imaginable. Chronic users of benzodiazepines require very precise tapering to avoid seizure, severe anxiety, and in some cases even death. In this write-up I intend to share methods that may be able to reduce dependency, delay tolerance build up, and reduce withdrawal symptoms. So far I’ve found two clinically backed ways of doing so, although I’m sure there are other methods found through anecdotal experiences. Feel free to message me on discord @restlessforthebag or you can email me at [email protected], I may choose to add them in later if I feel there is enough evidence of their efficacy.

Before we get into this, I would like to share another write up I did on etifoxine to replace benzodiazepines and reduce withdrawal. If you haven’t started benzos, please try this first. It’s a much safer alternative that, although not as strong, doesn’t have any withdrawal or negative effects on cognition.
https://rentry.co/etifoxinebenzos

The first method is a bit extreme and is probably not viable for most since the compound being used isn’t readily available, although I may be able to assist in acquiring an alternative. This study was performed on Rhesus monkeys given daily diazepam administration. Every third day they were given a dose of flumazenil, which you may recognize as a treatment for benzodiazepine overdose. Each time this antagonist was administered, it resulted in the monkeys returning to a drug naive state, meaning their tolerance and dependence was severely reduced. It also drastically reduced the withdrawal symptoms following diazepam discontinuation [1]. Repeating this in a recreational setting shouldn’t be too difficult because even in the high doses withdrawal was mitigated. At human equivalent doses, the highest doses used would be around 175mg of diazepam for the average American male, and 150mg for the average American female. This is equivalent to around 12mg and 10mg of alprazolam respectively. Even at these doses the withdrawal was severely reduced, and presumably tolerance as well. If you want to utilize this strategy administer an intranasal dose of flumazenil 2-3 times a week. The dose used in the study was ridiculously high, but I believe just a normal dose would work. If you choose to try this out, please let me know how it goes.

The next method is significantly more accessible, easy, and results in less potential adverse effects. Before I begin, I want you to know about neurosteroids. Neurosteroids are hormones made the adrenals, the gonads in men, and the ovaries in women. They serve many different functions that I won’t get into, it would make this guide far too long. If you want to research them more, it’s a fascinating topic and I highly recommend you do so. What we mainly want to focus on are the ones derived from pregnenolone and progesterone, since many of them have direct effects on the gabaergic system, some even functioning very similar to benzodiazepines [2]. One study explored how a large range of neurosteroids interact with benzodiazepines. They found that allopregnanolone, pregnenolone, and progesterone all prevent tolerance build up and heavily reduced when administered triazolam. The dose given was equivalent to 1.8mg for the average American male and 1.5mg for the average American female. If you know anything about triazolam, that’s quite the hefty dose. You would expect pretty severe withdrawal and certainly some tolerance build up, but the mice didn’t experience that because of the coadministration with these neurosteroids [3]. If you want to recreate you could just take some pregnenolone you bought off Amazon, but I don’t recommend that. Pregnenolone has a plethora of metabolites, many of which will do more harm than good if you’re trying to prevent benzodiazepine tolerance and withdrawal. My recommendation is allopregnanolone. One reasons is that allopregnanolone is an anxiolytic and gabaergic in of itself, it functions somewhat similarly to benzodiazepines [4]. This means you may be able to not only prevent tolerance build up, but also potentially lower your dose of your benzodiazepine(s). The human equivalent dose used in the study was 0.02025-0.0405mg/kg, or 1.8-3.6mg for the average American man and 1.5-3mg for the average American woman. Unfortunately, these doses would have to be injected, as the oral bioavailability of allopregnanolone is virtually zero. However, some have had success with topical and nasal administration. This thread is relevant for this, and has the link for the only allopregnanolone source that I know of. https://raypeatforum.com/community/threads/allop-liquid-allopregnanolone-for-lab-r-d.41055/ . You could also check out etifoxine which has been proven to raise allopregnanolone levels, and also synergizes very well with benzodiazepines. I have a write-up on it that I linked in the second paragraph.

Final Thoughts

Please understand that this is not medical advice. I’m a random 18 year old without any form of formal education regarding pharmaceuticals. These compounds can be incredibly dangerous and should be treated with much respect. Remember that you’re just a human, you aren’t invincible. You can be a victim of addiction or overdose, even if you don’t think it. Anyways, thanks for reading.

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Sources and their Relevance

[1] Flumazenil is able to return diazepam treated monkeys to a drug-naive state and reduces withdrawal symptoms
https://pubmed.ncbi.nlm.nih.gov/3102259/

[2] General overview of neurosteroids and their biological functions
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3139029/#:~:text=Neurosteroids%20are%20steroids%20synthesized%20within,are%20synthesized%20in%20the%20brain.

[3] Certain neurosteroids prevent benzodiazepine tolerance and reduce withdrawal symptoms.
https://europepmc.org/article/med/9385589

[4] Allopregnanolone is a GABA-A PAM and has anxiolytic effects
https://onlinelibrary.wiley.com/doi/10.1002/syn.21978

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Pub: 30 Jul 2023 02:16 UTC

Edit: 30 Jul 2023 03:05 UTC

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