Greetings Travelers,
One day, I promise to compile a comprehensive overview of my near-decade of experiences with a matrix of psychoactive compounds. Today, however, I would like to prevent an experience report for a most peculiar compound. This post is well over a year in the making and, unless I am mistaken, I am the only human being who has experience Imidazenil.
So how did we get here?
There are many researchers on the nootropics subreddit well known for their extensive knowledge regarding GABA based anxiolytics. Their posts, which are easy to search for, piqued my interest which quickly propelled into a passionate obsession. I will avoid delving too much into my interest in GABA based anxiolytics but years of seeing friends lost to alcohol, watched others spiral out on certain benzodiazepines, reading Phenibut withdrawal horror stories, and, at the end of the day, feeling very not alone in wanting a better, safer, therapeutic anxiolytic.
Enter GABAA positive allosteric modulators
This excellent post written by u/CL20 was perhaps my first exposure to understanding benzodiazepine agonism/antagonism and the subunits of GABAA. I highly encourage everyone reading this to read his overview of GABAA subunits. The salient note is that agonism of the GABAA a1 subunit is most susceptible to tolerance buildup and addiction as well as responsible for sedation and memory impairment.
Further reading:
Valium without dependence? Individual GABAA receptor subtype contribution toward benzodiazepine addiction, tolerance, and therapeutic effects
From Wikipedia:
Imidazenil[1] is an experimental anxiolytic drug which is derived from the benzodiazepine family, and is most closely related to other imidazobenzodiazepines such as midazolam, flumazenil, and bretazenil.
Imidazenil is a highly potent benzodiazepine receptor partial agonist[2] with an unusual profile of effects, producing some of the effects associated with normal benzodiazepines such as anticonvulsant and anxiolytic effects, yet without any notable sedative or amnestic[3] effects. In fact, Imidazenil blocks the sedative effects of diazepam, yet without lowering the convulsion threshold,[4] and so potentially could be a more flexible antidote than the antagonist flumazenil which is commonly used to treat benzodiazepine overdose at present.
Imidazenil has not yet been developed commercially for use in humans, however it has been suggested as a safe and effective treatment for anxiety,[5] a potent yet non-sedating anticonvulsant which might be particularly useful in the treatment of poisoning with organophosphate nerve agents,[6][7] and as a novel treatment for schizophrenia.[8]
Experience:
The synthesis for Imidazenil was not easy or quick. Nevertheless, I received a tested batch of the compound and have been evaluating it at various dosages. In my experience, the literature appears accurate. Here are my key takeaways after several weeks of near-daily use at various dosages, but mostly 500mcg-1.5mg. I rarely felt the need to increase my dosage beyond:
It is nice to finally experience another “next-generation” compound since the NSI-189, Dihexa, and P21 days. I realize this will be flagged as “high-risk” (as it should be), but as someone who previously vilified benzodiazepines and never considered seeking them out, I please encourage the more responsible members of this community to realize what this compound may mean for the safety of millions seeking relief from anxiety.
This is truly a special compound that is an improvement to traditional benzodiazepine anxiolytics in every way I can think of. By no means am I planning on staying on this for the rest of my life, but out of all my experiences with the subject matter related to this sub, this has been by far the most rewarding, interesting, and potentially game-changing discovery.
One day, I promise to compile a comprehensive overview of my near-decade of experiences with a matrix of psychoactive compounds. Today, however, I would like to prevent an experience report for a most peculiar compound. This post is well over a year in the making and, unless I am mistaken, I am the only human being who has experience Imidazenil.
So how did we get here?
There are many researchers on the nootropics subreddit well known for their extensive knowledge regarding GABA based anxiolytics. Their posts, which are easy to search for, piqued my interest which quickly propelled into a passionate obsession. I will avoid delving too much into my interest in GABA based anxiolytics but years of seeing friends lost to alcohol, watched others spiral out on certain benzodiazepines, reading Phenibut withdrawal horror stories, and, at the end of the day, feeling very not alone in wanting a better, safer, therapeutic anxiolytic.
Enter GABAA positive allosteric modulators
This excellent post written by u/CL20 was perhaps my first exposure to understanding benzodiazepine agonism/antagonism and the subunits of GABAA. I highly encourage everyone reading this to read his overview of GABAA subunits. The salient note is that agonism of the GABAA a1 subunit is most susceptible to tolerance buildup and addiction as well as responsible for sedation and memory impairment.
Further reading:
Valium without dependence? Individual GABAA receptor subtype contribution toward benzodiazepine addiction, tolerance, and therapeutic effects
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5973310/pdf/ndt-14-1351.pdfIn the light of current evidence, α1 dormant, α2, α3, and α5 subtype partial agonists not only possess low abuse potential but are also low or devoid of tolerance building. There is evidence that α1 containing GABAA receptors directly contributes to the downstream effects of tolerance because α1 (H101R) mice have been shown to maintain expressions in neuroplasticity-coding transcripts after diazepam administration.120 This perfectly agrees with data from animal studies regarding the lack of tolerance in α1 subtype inactive compounds such as TPA023B and imidazenil.121–126 Future drug discovery involving tranquilizers should look for partial agonists of α2 , α3 , and α5 containing GABAA receptors; Valium without its side effects is potentially achievable.
From Wikipedia:
Imidazenil[1] is an experimental anxiolytic drug which is derived from the benzodiazepine family, and is most closely related to other imidazobenzodiazepines such as midazolam, flumazenil, and bretazenil.
Imidazenil is a highly potent benzodiazepine receptor partial agonist[2] with an unusual profile of effects, producing some of the effects associated with normal benzodiazepines such as anticonvulsant and anxiolytic effects, yet without any notable sedative or amnestic[3] effects. In fact, Imidazenil blocks the sedative effects of diazepam, yet without lowering the convulsion threshold,[4] and so potentially could be a more flexible antidote than the antagonist flumazenil which is commonly used to treat benzodiazepine overdose at present.
Imidazenil has not yet been developed commercially for use in humans, however it has been suggested as a safe and effective treatment for anxiety,[5] a potent yet non-sedating anticonvulsant which might be particularly useful in the treatment of poisoning with organophosphate nerve agents,[6][7] and as a novel treatment for schizophrenia.[8]
Experience:
The synthesis for Imidazenil was not easy or quick. Nevertheless, I received a tested batch of the compound and have been evaluating it at various dosages. In my experience, the literature appears accurate. Here are my key takeaways after several weeks of near-daily use at various dosages, but mostly 500mcg-1.5mg. I rarely felt the need to increase my dosage beyond:
- A tremendous reduction in anxiety and ruminating thoughts. Very direct and targeted in this regard. If I could compare the anxiolytic effects to anything, I find 1mg of Imidazenil to be akin to ~1g of Phenibut combined with 50mg of Fasoracetam.
- No noticeable tolerance buildup whatsoever. Does not appear to synergize with alcohol….at all? THIS IS EXTREMELY ILL-ADVISED so please stay safe and don’t be stupid. However, I find Imidazenil appears to increasemy tolerance to alcohol rather than decrease it. While I am obviously on the more cavalier side of this community, there is something about the effects of this compound that do not compel me to increase the dosage. I found the Goldilocks zone out of the box and have essentially stayed there.
- Potential restoration of tolerance for other GABAergic compounds.
- I never experienced any loss of coordination, amnesia, or hypnotic effects. Again, it echoes the nootropic aspects of Fasoracetam.
- Definite and noticeable dopaminergic modulation. This compound plays excellently with all stimulants I combined it with, from pre-workouts to phenidates. Akin to caffeine + L-Theanine, Imidizaneil + DRIs produce a much less jaggy experience. It almost reminds me of certain effects with low-dose Naltrexone.
- Paradoxical effects on energy. It wakes me up in the morning while nuking fogginess. It helps me fall asleep quicker and stay asleep.
- Increased libido and performance in the bed very similar to Phenibut. I have not noticed increased libido from any other GABAergic that I can think of.
- Discontinuation without tapering for over a week with no ill-effects.
- I am significantly less chatty on this compound. In social situations, I am clearly engaged but rather quiet. This is atypical for me.
It is nice to finally experience another “next-generation” compound since the NSI-189, Dihexa, and P21 days. I realize this will be flagged as “high-risk” (as it should be), but as someone who previously vilified benzodiazepines and never considered seeking them out, I please encourage the more responsible members of this community to realize what this compound may mean for the safety of millions seeking relief from anxiety.
This is truly a special compound that is an improvement to traditional benzodiazepine anxiolytics in every way I can think of. By no means am I planning on staying on this for the rest of my life, but out of all my experiences with the subject matter related to this sub, this has been by far the most rewarding, interesting, and potentially game-changing discovery.