bigzip44
Bluelighter
- Joined
- Aug 29, 2009
- Messages
- 94
I think this is the perfect nook of bluelight to post this in and I think you guys will have a time deciphering this question.
1. Ibogaine promises to not only knock out withdrawals but also to "reverse addiction" which seems strangely vague to me
2. There is now a consensus among ALL responsible ibogaine providers that one must be off of bupe for AT LEAST 2 months, probably 3, for the ibogaine to work its magic
3. The reason for the above is stated as this ^ you will find buprenorphine and its metabolites (norbuprenorphine, etc) far after its half-life would indicate that the drug has left your body: reasoning being that subutex binds so strongly with your fat-soluble lipids that measuring plasma for half-life in no way can accurately indicate whether or not bupe and its metabolites are still floating around your receptors
I will attach an article written by someone that explains this all far better than I could for you to look at but the basic question is this: what is the deal with buprenorphine causing ibogaine to lose its magical powers of opiate addiction reversal, etc. Thank you for your patience with my lay understanding and description of the issue at hand, but I would really like someone to look at this, although I'm sure several people already are, just not people that have anything to do with the powers that be. Below you will find the paper I mentioned above. Thank you for your time.
To be presented at the Fourth Annual Ibogaine Providers Conference in Durban, South Africa. For Erika Florianova
OBJECTIVE
The aim and purpose of the Suboxone Papers is to provide a concise introduction to the neurobiological agents, buprenorphine and ibogaine, their metabolites, and how they relate to each other.
The Suboxone Papers are structured into a monologic conversation in order to evoke stream of consciousness inside the realm of thought.
You are cordially invited to join the discussion, raise questions, and explore the theoretical architecture below, so that all of us may increase our understanding of one another’s point of view. Furthermore, so that we may recognize the potential range of possible perspectives available involving a subject we collectively share an interest in.
~~~~~~~~~~~~~~ AGENT IDENTIFICATION ~~~~~~~~~~~~~~ BUPRENORPHINE
aka SUBUTEX
or
SUBOXONE (w/Naloxone)
Originally researched clinically and presented as a rapid opioid taper therapy system.
CURRENTLY EMPLOYED FOR:
The treatment of moderate to extreme pain.
Perioperative analgesia, employed throughout the three phases of operative surgery, (preoperative, intraoperative, postoperative).
Long term replacement therapy for opioid dependence.
NOTE: Thematically, the following presentation of idea & thought places focus on the physiological results that the agent of interest, buprenorphine evokes in the neurobiology of a long term user such as the opioid dependent individual involved in a Suboxonebased opioid replacement therapy program.
SERPENTS AND SILHOUETTES IN THE GARDEN OF EDEN
Buprenorphine, a synthetic opioid analgesic derived from thebaine, interacts predominantly with the μopioid receptor applying a longer duration of action than organic alkaloids such as morphine.
Buprenorphine is a partial agonist, more specifically described as an agonist/antagonist.
The agent yields partial agonist characteristics at the μopioid receptor while acting as an antagonist at the κopioid receptor.
Buprenorphine aggressively binds to opioid receptor sites, territorially occupying μ, κ, and δ, also referred to as the mu (MOR), kappa (KOR) and delta (DOR) opioid receptor sites.
Buprenorphine’s binding effects at the μ and the κopioid receptor causes a reduction in neuronal excitability resulting in hyperpolarization. Being extremely lipophilic, it is thoroughly distributed throughout adipose tissue in the body.
Buprenorphine has the ability to cross into breast milk; as well as the ability to enter tissue in the placenta. Metabolically, buprenorphine undergoes both Ndealkylation into norbuprenorphine and glucuronidation.
Norbuprenorphine, a major metabolite of buprenorphine, has onefifth of the pharmacologic activity of its parent compound, and successfully undergoes the process of glucuronidation.
VISUALIZE
The elements that envelop your world as a child
The simple things in life A cinematic flow
Eventually you fall from a staircase and awake in a hospital bed Sterilized walls A picture book left by your family lays next to your pillow
A nurse walks in with a plastic smile, injects your medication intravenously
Sickness and sorrow permeate the air
Welcome to a new world
THE UNIQUE AND INNOVATIVE USE OF BUPRENORPHINE AS A NOVEL TAPERING AGENT
In a rapid opioid tapering protocol, buprenorphine binds strongly to three cerebrally located opioid receptors. Specifically, the μopioid receptor, which is known for neurally signaling analgesic effects and sedating acute withdrawal associated with abrupt opioid cessation.
Reducing levels of buprenorphine daily (utilizing 7 & 13 day tapers), causes an internal taper to continue in the body at a slow rate for an extended number of weeks.
One could compare the beneficial results of this type of extended reduction activity to the results historically associated with users who employ “tapers.” Tapers include a variety of dose descending protocols in which a user continuously reduces their intake of a short acting opiate (such as heroin) by a fractional amount daily. The user eventually ceases opiate use altogether after a specific number of days or weeks, thus minimizing the discomfort associated with acute and post acute withdrawal.
Chronic administration of Suboxone leads to an accumulation of buprenorphine reserves in fatty tissues. This compounding is informally referred to as “stacking.”
Buprenorphine is highly lipid soluble and not very water soluble. Upon crossing the blood brain barrier the agent binds to plasma proteins.
This type of initial binding activity is a common circulatory distribution mechanism for lipid soluble agents. Buprenorphine will then dissociate from the plasma protein and dissolve into the lipidrich brain tissue.
EYES THAT KILL
It is important to note that buprenorphine will systemically bind to lipidrich territory, specifically accumulating in areas where orbital fat is located.
Theoretically, accumulated quantities of buprenorphine stored in orbital fat, compounded in lipids over extended periods of time, could contribute to a partial loss of mobile function in the muscles responsible for modulating the optic nerve during general eye motion.
Therefore, it is possible that these compounded amounts of buprenorphine accumulated in areas rich in orbital fat, may weaken the lubricating quality of an already sensitive lipidrich neurological system.
Muscles responsible for supporting and controlling movements of the optic nerve employ this lubricating characteristic throughout all the mechanics involved in mobile function. This quality may be described as the defining characteristic of orbital fat.
Buprenorphine saturation in this lipid rich area could be causing a distortion in the supportive quality of the orbital fat at the cellular level, thus catalyzing the commonly experienced and frequently occurring migraineresembling pain associated with longterm use in patients undergoing Suboxone replacement therapy.
VISUALIZE
An aesthetically infected beauty queen, obsessed with her own image is forever transfixed in the vanity mirror. Reflections of her superiority reign supreme.
SUBOXONE SATURATION ALONG ADIPOSE ARCHITECTURE POISONING THE WISHING WELL
Coordination entities, also known as ligands, function as battery packs in the brain; operating like conductive magnetic units that complete neurological circuitry deep within cerebral tissue.
These entities are also known as ligandreceptor complexes
Both buprenorphine and ibogaine metabolites compound and affect lipid density imbedded in neural tissue. Ligands occupy each receptor for a finite period of time eventually detaching from the receptor. Relative concentrations in brain tissue and plasma are in an equilibrium. Relative concentrations leave two possible variant results. When plasma concentrations are high, mass action drives the agent into the brain. When concentrations in plasma are low, buprenorphine leeches out of the brain.
Exogenous substances such as opioid agents are excreted through the body’s defense mechanisms mainly through urine and bile at a certain rate that varies with each compound, along with micromolar (μM) amounts being eliminated through dermal pores.
Therefore, upon administering a dose of a buprenorphine, plasma levels increase in the user. During this interval of intake activity, the clearance mechanism cannot keep up with the input.
When plasma levels are high, circulation distributes the buprenorphine systemically, dissolving the agent into tissue lipids throughout the body.
Most of a given dose does not reach its intended target, but ideally, enough gets to the intended target to cause a therapeutic effect. As the clearance mechanisms eventually lower plasma concentrations, drugs are repartitioned into the bloodstream and removed from tissues.
In human pharmacology, the rate of drug clearance is expressed as “plasma halflife.” Plasma halflife refers to the amount of time it takes for the clearance mechanisms to cut the plasma concentration in half. This is measured most commonly through the comparison of serial blood tests. In general, this method is a clinically accepted diagnostic system utilized for detecting approximate levels of an agent’s binding activity at the intended receptor embedded in biological tissue.
It is possible to directly measure receptor binding in vitro by grinding up animal tissue and using sophisticated chromatography and/or radioimmunoassay tools. However, this is never done with humans. Instead, plasma halflife is compared to receptor binding kinetics in lab animals. Therefore, it is assumed that the human ratio would be about the same.
Clinical researchers currently measure plasma levels only, if measuring anything at all.
Widely circulating research articles repetitively suggest that buprenorphine will not be bound to the μopioid receptor after four to seven days following cessation of drug ingestion.
This phrasing implies that you have directly measured the μopioid receptor site’s tissue binding levels (i.e., ground and desiccated a human brain, recently in vitro/deceased).
The reality at hand is clearly much different than what the latter implies. A scientific suggestion of this
nature is hypothetically based on speculation that five plasma halflives for buprenorphine equivalates to four to seven days. This refers to the period of time it usually takes for plasma and tissue levels to go below the effective drug binding affinity, thus causing the remainder of the drug to stop working.
It should be noted, in the field of clinical research and discovery, plasma concentrations are actually a surrogate for tissue binding.
This is considered valid for single doses of any drug and for continuous dosing of watersoluble drugs. However, for the individual interested in undergoing ibogaine treatment, one should recall the fact that buprenorphine is highly lipid soluble.
Meaning, the equilibrium parameters favor partitioning of the agent into lipidic tissues rather than into plasma.
Humans have an average blood volume of five liters and an average (nonwater) tissue volume of approximately twenty liters.
If buprenorphine tends to concentrate in the tissues, which are of themselves a greater volume than the plasma, simply looking at plasma concentrations provides a significant underestimate of the actual quantity of the buprenorphine stored in the body.
Pharmacologists express this as “volume of distribution” (VoD). This signifies the amount of water
necessary if the total amounts of the drug in the body were dissolved in water at the measured plasma concentration. Buprenorphine VoD is one hundred and fifty five liters. Since psychoactive drugs must be lipid soluble to enter the brain, they all have large VoDs. For example, the VoD of highly watersoluble aspirin, is seven liters.
Due to lipid partitioning, plasma concentrations of chronicallyadministered lipid soluble drugs may significantly underestimate the total amount of the drug in the body. Due to the effects of drugs requiring the presence of a certain tissue concentrations to affect receptor binding, the possibility of underestimation is not as problematic as it may seem. Most drugs don’t bind to receptors at 1/10 or 1/100 of their effective concentrations, research can ignore the long tail of drug elimination due to lipid partitioning in most cases. However, some drugs bind to multiple receptors, each one with a different binding affinity. It might take micromolar concentrations to elicit the desired clinical effects on receptor A, but only 0.01 micromolar concentrations to activate receptor B which has either no clinical effects or may even cause adverse effects.
Therefore, it is possible that very low plasma concentrations of buprenorphine can persist for many weeks after the last dose. It takes this long for the large lipid stores to leech into the circulation and be eliminated. It is also possible that, although these concentrations are too low to give clinical benefit, they may be able
to bind to a different receptor and cause adverse effects. The majority of drugs that make it through the FDA gauntlet don’t cause adverse effects at subtherapeutic concentrations. However, if buprenorphine is combined with certain other drugs, then the combination of receptor binding patterns could possibly cause adverse effects, even at nearly invisible plasma concentrations of buprenorphine.
Results such as these could only be determined empirically, through clinical observation. The FDA requires manufacturing companies to look for drug to drug interactions between their candidate compound and a varied panel of widelyused medications. However, the FDA does not require that all possible combinations be tested before marketing. In particular, the FDA does not require testing of the interactivity of illicit or controlled compounds with their chosen drug candidates.
VISUALIZE
Ligands compound collectively, saturating designated territories like recentlyreleased renegade prisoners of war. Occupying the enemy’s capital, adrenaline fueled soldiers ravage reserves, eventually crushing the coalition’s ability to communicate clearly within the core.
MONARCHY AMONGST THE METABOLITES, SURPASSING THE PREDECESSOR PHANTOMS IN THE SHADOWS, THE EVERLASTING OPERA
Buprenorphine is extensively metabolized in humans. Excretion of the parent compound in urine is minimal.
Urine analysis is commonly relied upon when trying to detect "clean time" or drugfree time zones.
Drugfree time zones are intervals of time when a patient is considered safe from the interference effects of a recently ceased psychoactive drug, (i.e. fat soluble compounds that have been continuously ingested passed the point of reaching "steadystate" levels in plasma concentrations). Biologically,
a user of buprenorphine reaches steadystate levels at day seven.
Buprenorphine has ceiling effects with respect to analgesia and respiratory depression.
Norbuprenorphine is a dealkylated metabolite of its parent compound.
Norbuprenorphine, unlike its parent compound, is a potent opioid agonist, with high affinities for all three opioid receptors μ, κ, and δ.
As evidenced in rat tissue, norbuprenorphine functions as a full agonist
and causes full respiratory depression through rapid binding at the μreceptor.
Norbuprenorphine respiratory depression was opioidreceptor mediated, and also antagonized by buprenorphine.
Norbuprenorphine showed ten times the potency of buprenorphine.
The parent compound's major metabolite also showed respiratory depressant effects in sheep.
In humans, normal hepatic function metabolically eventuates buprenorphine into three major metabolites, norbuprenorphine, buprenorphine3glucuronide, and norbuprenorphine3glucuronide.
Clinical studies have detected plasma concentrations of the three major metabolites in humans.
Peak plasma concentrations of the three major buprenorphine
metabolites met the equivalent or exceeded those of the parent compound.
The following data presents molar area under the concentration in plasma versus time curve following a single dose of buprenorphine:
Norbuprenorphine showed 200% higher plasma concentrations than those of buprenorphine.
Buprenorphine3glucuronide showed 100%, higher plasma concentrations than those of buprenorphine.
Norbuprenorphine3glucuronide showed 600% higher plasma concentrations than those of buprenorphine.
Metabolism of buprenorphine to norbuprenorphine was originally considered to be an inactivation pathway.
An inactivation pathway can be described as the metabolic function
that renders a chemically reactive compound into an inactive compound.
Clinical evidence is now suggesting that the dealkylation of buprenorphine
to norbuprenorphine is in actuality a bioactivation pathway. A bioactivation pathway is the metabolic transformation in which a relatively inactive precursor
produces a compound that is chemically reactive.
Current status of buprenorphine glucuronide metabolites pharmacology in humans: {{{undefined}}}
VISUALIZE
A shadow personality mimics your every move. Mocking your motions like a mime artist cascading your image throughout endless halls of mirrors. There is no escaping her reflective behaviour.
Naturally, upon realizing you are no longer unique or original, you become selfconscious.
Stifling your ability to reach your objective you fail to occupy your destination point.
COMPOUNDING THROUGHOUT CAVITIES IN THE CATHEDRAL CREATIVE OCCUPYING THE ENDLESS HOURGLASS
Systemically speaking, ibogaine is a very userfriendly compound. Once transported to the liver for metabolic manipulation, the Odemethylation process initiates its catalyzation through polymorphic expression of CYP2D6. 12hydroxyibogamine, also known as noribogaine, is born out of this metabolic process of biotransformation. It has been further proposed that ibogaine is deposited into adipose tissue and then further metabolized into noribogaine following its release back into the plasma.
Clinical studies show that ibogaine does not agonize or antagonize μ and κopioid receptor sites. Noribogaine, however, showcases a binding profile with site specific differences than that of its parent compound. Clinical research studies have found that noribogaine shows higher plasma levels than ibogaine. Noribogaine is also detectable for a duration of time far exceeding the time period associated with its parent compound. Noribogaine is more potent than ibogaine in rat brain drug discrimination assays when tested for the subjective effects of ibogaine. The desmethyl metabolite may act as key equilibrium preserver, maintaining neurological harmony through its possible reassociation with the μ and κopioid receptor sites.
Clinical studies show that ibogaine binds with low micromolar μMaffinity to a multitude of molecular targets within the central nervous system, resulting in a unique complex pharmacology. The ibogaine alkaloid binds with μ and κopioid receptors, sigma2 receptors, NMDAcoupled ion channels, serotonin and dopamine transporters...The list goes on and on in regards to the parent compound’s activity. Simultaneously, noribogaine subdues opioid withdrawals at the κ and μopioid receptors. Assuming, of course, that ibogaine is properly allowed to enter adipose tissue, preserving the ability to metabolize into noribogaine through future metabolic activity.
Researchers tend to agree that the synergistic result of ibogaine and noribogaine is necessary to deliver the successful benefits associated with ibogaine treatment when employed as an opiate addiction interrupter. Researchers propose that there are many areas of the brain that may be affected by ibogaine and noribogaine that are unknown at this time. The direct biological function of ibogaine and noribogaine may continue to be a neurological mystery until empirical data can be realized. Don’t hold your breath.
What would happen if buprenorphine saturated lipidrich tissue and had reached maximum capacity through long term ligand compounding due to continuous dosing at steady state plasma levels?
How long could buprenorphine’s metabolic offspring generationally reassociate with κ and μopioid receptors once a user’s daily doses of the medication have ceased?
Would ibogaine be able to enter fatty tissue once released from the liver with buprenorphine metabolites having saturated fatty tissue at maximum capacity?
Would a Suboxone user only experience partial effects of the ibogaine experience if undergoing treatment with only having abstained from medication for a limited time prior to ibogaine therapy?
VISUALIZE
As the wartorn father walks out on his family, turning his back on the past, he disappears into the horizon, facing the setting sun.
The father’s silhouette fades smaller and smaller into the distance, all the while his youngest son grows taller and taller, in his predecessor’s shadow.
KAPPA
A LANDSCAPE EMBEDDED IN MYSTERY
A discretely located opioid receptor with the ability to modulate breathing patterns and rhythms rests awaiting activity. Controversial, in relation to the contradictory findings, regarding the differences in activity characteristics and signal pathway expression, currently remains to be completely understood.
THOUGHT
Opiate induced hypnagogia is directly or indirectly related to agonist activity at the kappa opioid receptor.
Opiate induced agonist activity at at the kappaopioid receptor site has produced oneiric visionary states, cinematic vignettes of dream sequencing as well as the more classically described fullblown hallucinogenic experiences.
Multiple κopioid receptor agonists, as well as, both the selective κopioid receptor agonists and specific κopioid receptor antagonists can produce disassociation, dysphoria, and states of hallucination in subjects undergoing clinical research and investigation.
It is possible that noribogaine agonism at the κopioid receptor is responsible for initiating the rapid eye movement activity associated with the self introspection one experiences following the ingestion of sufficient quantities of iboga extracts during what is commonly referred to as the dreamstate phase of treatment. It will likely take hundreds of clinical studies, before we truly understand the mechanisms of action responsible for determining the ibogaine alkaloid’s multitude of actions at serotonin receptors (reuptake), blockading nicotinic channels, not to mention all the rest of the action found throughout neural territory possibly responsible for catalyzing the ignition of the psychoactiveinduced state commonly referred to as the waking dream.
Hypnagogia: agōgos "leading, guiding, inducing", pompe "act of sending", hypnos “sleep”
The experience of the transitional state that spans from moment to moment wakefulness to sleep including the varying levels of lucidity encountered in between.
Hypnagogic state a self reflective state of consciousness
VISUALIZE:
At sunset, a rutilated quartz held up to the sky illuminates the eye and captivates the viewer’s attention. Each facet catches and redirects the light illuminating darkened avenues and alleyways through a subtle twist of the wrist.
Find the “phantoms,” the imperfections related to the density grading of the stone that exist throughout the central core. Find the phantoms and find the the break between clarity and chaos.
IBOGAINE & SUBOXONE RECEPTOR SITE WARFARE
Ibogaine and its desmethyl metabolite...need to exist in union within their surrounding neural environment...lipidrich territories...allowing freedom of expression....allow ibogaine and noribogaine to function in harmony......freedom from monarchy........free enterprise.
COMPETITIVE INHIBITION : Occurs when two or more drugs compete for the same enzyme.
Clinical significance of inhibition interactions rely initially on relative concentrations of the compounds involved. Specific compounds have the ability to bind and act as competitive inhibitors of different CYP enzymes. These compounds can bind both irreversibly or reversibly, inhibiting other compounds from binding enzymatically.
Mechanism based inhibition manifests when compounds are metabolized by the CYP system into active metabolites. Binding to the enzyme, these metabolites cause an irreversible loss of function.
Once this binding occurs, new activity is regained only through the synthesis of new enzymes.
Complex mechanisms of inhibition may also occur as well. Compounds undergo metabolic activation by the CYP process into inhibitory metabolites. These metabolites may generate relatively stable complexes with CYP holding cytochrome in a state of inactivity. The clinical significance to this interaction is high, due to its extensive duration of time.
Inhibition is achieved once the inhibitor reaches steady state (which is four to seven halflives), and the maximum concentration of the inhibited compound occurs once the inhibited compound reaches steady state at its new, extended halflife.
The time frame necessary to allow for the interaction to resolve itself greatly depends on halflives the compounds as well as the halflives of their active metabolites.
VISUALIZE
Strolling by a carousel spinning slowly as the evening sky loses light, you decide on a carnival ride.
Paying for a ticket, you enter an empty shadow lane.
As your chariot climbs into the darkness above, you look to your left and see that a carnival clown has hung himself...roped all the way up, swings low from the rafters. Eyes painted, little circles.
His body appears to be floating in space. Rusted hinges scrape and bounce off the rafters, echo their reflections throughout the open emptiness. Just a joke you say to yourself. A bad one. Looking down to the ground you notice that he’s sabotaged the track at top of the final drop.
A candle light left flickering in the corner, so you’d be sure to see his work one last time.
CONCLUSION
ESTABLISHING EQUILIBRIUM
Since the introduction of buprenorphine to the global market and even more so, as it is currently employed, both providers and patients alike have explored a variety of questions regarding treatment options and comparing timeline strategies in the treatment of opioid dependency post buprenorphine based replacement therapy.
How can we assure the efficacy of ibogaine therapy applied in the case of an individual that has used the buprenorphine for seven or thirteen days and contrast that with someone who employed the agent daily for twelve months continuously? Where do we start to scale the time period of abstinence needed free from buprenorphine and prior to treatment with ibogaine?
When does an individual’s lipid structure reach maximum volume?
Could continuous chemical compounding into lipid tissue reach a maximum saturation level, not allowing weaker binding ligands to enter?
Once we consider all of the relative physiological characteristics such as medication taken in relation to body weight, metabolic function of the thyroid, hepatic function of the liver, cardiac function, etc...We are left in endless speculation.
THOUGHT
Let us break the discussion down to the one core question that most greatly affects a future ibogaine patient’s outcome post Suboxone replacement therapy.
CORE QUESTION
What is the specific length of time needed for a subject to be (neurobiologically) free from exogenous doses of buprenorphine prior to undergoing ibogaine therapy in order to assure the successful application of ibogaine’s therapeutic use as an addiction interrupter?
The answer to the question above may never be collectively agreed upon due to the nature of subjectivity regarding an exact number of days, weeks or months needed. A wide span of physiological characteristics would need to be determined prior to diagnosing a former buprenorphine user, or even manipulate an individual’s time span.
One classical tactic to employ, would be to look at the anecdotal reports and simply begin by adopting the idea that some people may need a much longer time span, free of buprenorphine exogenously fed into the lipid system.
Most therapy providers are looking for an approximate timespan where one can begin to look towards the future with confidence, thus plan and treat accordingly.
If ibogaine has no function as noribogaine through normal metabolic manifestation due to its inability to enter adipose architecture, does the human body eliminate the indole alkaloid through urine intact?
How long does it take buprenorphine take to clear from the adipose tissue sufficiently so as not to disturb the beneficial results that follow ibogaine therapy?
We know that certain factions recommend a twentyone day preparation phase, others predict that a sixty or even a ninety day period of time away from buprenorphine is probably more appropriate.
All we know right now, is that no one knows.
Most ibogaine therapy practitioners tend to agree that although it may be uncommon and even rare, there are patients that have needed extensive durations of time buprenorphinefree in order to inherit the beneficial effects of ibogaine therapy following their treatment.
Patients report extended periods of post acute withdrawal symptoms persisting post ibogaine therapy sessions; some for many months following treatment.
A number of these patients return to centers for a second treatment or obtain ibogaine through internet vendors and administer themselves at a later date, after researching the residual effects of buprenorphine interfering with the efficacy of ibogaine.
Many of these questions may never be answered definitively; until empirical evidence emerges at some future date. This could obviously take a while.
Accepting this as the current reality we could simply begin by adopting a classical perspective; plant the seeds of thought leaving them open to evolve organically.
We could discard the idea of the need for empirical evidence and begin to explore the world of theoretical possibilities; continuing to discuss the possibilities that could interfere with the efficacy of ibogaine therapy.
Eventually we may notice that a further branching out of communication within our community emerges. And, rooted in confidence that the earth will provide her support, watch her take on a life of her own and bear fruit.
© Lex Kogan, 2014
RESOURCE REFERENCES
NOTE
The author of The Suboxone Papers has chosen to present the conference version of the above work free from numerical referencing (academia) in order to preserve the material’s monologic integrity.
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[26] Toutain P, & BousquetMélou A., “Plasma terminal halflife”, J Vet Pharmacol Ther. , 2004 Dec;27(6):42739.[27] “Basic Pharmacokinetics”, Concepts in Clinical Pharmacokinetics, http://www.ashp.org/doclibrary/bookstore/p2418chapter2.aspx [28]Dillon, S., & Gill, K., “Basic Pharmacokinetics”, Rates of Reaction, http://www.pharmpress.com/files/docs/clinical_pharmacokinetics_samplechapter.pdf [29] Roth, LJ., & Barlow, CF., “Drugs in the Brain”, Science, 1961 Jul 7;134(3471):2231. [30] Masood N. Khan, John W. Findlay, ed., “Ligandbinding assays development, validation, and implementation in the drug development arena”. Hoboken, N.J.: John Wiley & Sons, (2009). [31] Brown SM1, & Holtzman M., Kim T., & Kharasch ED., “Buprenorphine metabolites, buprenorphine3glucuronide and norbuprenorphine3glucuronide, are biologically active”, Anesthesiology, 2011 Dec;115(6):125160. doi: 10.1097/ALN.0b013e318238fea0. [32] Villiger JW., “Binding of buprenorphine to opiate receptors. Regulation by guanyl nucleotides and metal ions”, Neuropharmacology, 1984 Mar;23(3):3735. [33]Wang D1, & Sun X., &Sadee W., “Different effects of opioid antagonists on mu, delta, and kappaopioid receptors with and without agonist pretreatment”, J Pharmacol Exp Ther., 2007 May;321(2):54452. Epub 2007 Jan 31. [34]Chang Y1, & Moody DE., & McCanceKatz EF., “Novel metabolites of buprenorphine detected in human liver microsomes and human urine”, Drug Metab Dispos., 2006 Mar;34(3):4408. Epub 2005 Dec 28. [35] Compton P1, & Ling W., Moody D., Chiang N., “Pharmacokinetics, bioavailability and opioid effects of liquid versus tablet buprenorphine”, Drug and Alcohol Dependence, 82 (2006) 2531.[36]Bruijnzeel, Adrie W., “Kappaopioid receptor signaling and brain reward function”, Brain Res Rev., December 2010. [37]Soichiro Ide, Masabumi Minami, Masamichi Satoh, George R Uhl, Ichiro Sora, & Kazutaka Ikeda, “Buprenorphine Antinociception is Abolished, but NaloxoneSensitive Reward is Retained, in Opioid Receptor Knockout Mice”, Neuropsychopharmacology (2004) 29, 1656–1663.

1. Ibogaine promises to not only knock out withdrawals but also to "reverse addiction" which seems strangely vague to me
2. There is now a consensus among ALL responsible ibogaine providers that one must be off of bupe for AT LEAST 2 months, probably 3, for the ibogaine to work its magic
3. The reason for the above is stated as this ^ you will find buprenorphine and its metabolites (norbuprenorphine, etc) far after its half-life would indicate that the drug has left your body: reasoning being that subutex binds so strongly with your fat-soluble lipids that measuring plasma for half-life in no way can accurately indicate whether or not bupe and its metabolites are still floating around your receptors
I will attach an article written by someone that explains this all far better than I could for you to look at but the basic question is this: what is the deal with buprenorphine causing ibogaine to lose its magical powers of opiate addiction reversal, etc. Thank you for your patience with my lay understanding and description of the issue at hand, but I would really like someone to look at this, although I'm sure several people already are, just not people that have anything to do with the powers that be. Below you will find the paper I mentioned above. Thank you for your time.
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THE SUBOXONE PAPERS Lex Kogan May 2014
To be presented at the Fourth Annual Ibogaine Providers Conference in Durban, South Africa. For Erika Florianova
OBJECTIVE
The aim and purpose of the Suboxone Papers is to provide a concise introduction to the neurobiological agents, buprenorphine and ibogaine, their metabolites, and how they relate to each other.
The Suboxone Papers are structured into a monologic conversation in order to evoke stream of consciousness inside the realm of thought.
You are cordially invited to join the discussion, raise questions, and explore the theoretical architecture below, so that all of us may increase our understanding of one another’s point of view. Furthermore, so that we may recognize the potential range of possible perspectives available involving a subject we collectively share an interest in.
~~~~~~~~~~~~~~ AGENT IDENTIFICATION ~~~~~~~~~~~~~~ BUPRENORPHINE
aka SUBUTEX
or
SUBOXONE (w/Naloxone)
Originally researched clinically and presented as a rapid opioid taper therapy system.
CURRENTLY EMPLOYED FOR:
The treatment of moderate to extreme pain.
Perioperative analgesia, employed throughout the three phases of operative surgery, (preoperative, intraoperative, postoperative).
Long term replacement therapy for opioid dependence.
NOTE: Thematically, the following presentation of idea & thought places focus on the physiological results that the agent of interest, buprenorphine evokes in the neurobiology of a long term user such as the opioid dependent individual involved in a Suboxonebased opioid replacement therapy program.
SERPENTS AND SILHOUETTES IN THE GARDEN OF EDEN
Buprenorphine, a synthetic opioid analgesic derived from thebaine, interacts predominantly with the μopioid receptor applying a longer duration of action than organic alkaloids such as morphine.
Buprenorphine is a partial agonist, more specifically described as an agonist/antagonist.
The agent yields partial agonist characteristics at the μopioid receptor while acting as an antagonist at the κopioid receptor.
Buprenorphine aggressively binds to opioid receptor sites, territorially occupying μ, κ, and δ, also referred to as the mu (MOR), kappa (KOR) and delta (DOR) opioid receptor sites.
Buprenorphine’s binding effects at the μ and the κopioid receptor causes a reduction in neuronal excitability resulting in hyperpolarization. Being extremely lipophilic, it is thoroughly distributed throughout adipose tissue in the body.
Buprenorphine has the ability to cross into breast milk; as well as the ability to enter tissue in the placenta. Metabolically, buprenorphine undergoes both Ndealkylation into norbuprenorphine and glucuronidation.
Norbuprenorphine, a major metabolite of buprenorphine, has onefifth of the pharmacologic activity of its parent compound, and successfully undergoes the process of glucuronidation.
VISUALIZE
The elements that envelop your world as a child
The simple things in life A cinematic flow
Eventually you fall from a staircase and awake in a hospital bed Sterilized walls A picture book left by your family lays next to your pillow
A nurse walks in with a plastic smile, injects your medication intravenously
Sickness and sorrow permeate the air
Welcome to a new world
THE UNIQUE AND INNOVATIVE USE OF BUPRENORPHINE AS A NOVEL TAPERING AGENT
In a rapid opioid tapering protocol, buprenorphine binds strongly to three cerebrally located opioid receptors. Specifically, the μopioid receptor, which is known for neurally signaling analgesic effects and sedating acute withdrawal associated with abrupt opioid cessation.
Reducing levels of buprenorphine daily (utilizing 7 & 13 day tapers), causes an internal taper to continue in the body at a slow rate for an extended number of weeks.
One could compare the beneficial results of this type of extended reduction activity to the results historically associated with users who employ “tapers.” Tapers include a variety of dose descending protocols in which a user continuously reduces their intake of a short acting opiate (such as heroin) by a fractional amount daily. The user eventually ceases opiate use altogether after a specific number of days or weeks, thus minimizing the discomfort associated with acute and post acute withdrawal.
Chronic administration of Suboxone leads to an accumulation of buprenorphine reserves in fatty tissues. This compounding is informally referred to as “stacking.”
Buprenorphine is highly lipid soluble and not very water soluble. Upon crossing the blood brain barrier the agent binds to plasma proteins.
This type of initial binding activity is a common circulatory distribution mechanism for lipid soluble agents. Buprenorphine will then dissociate from the plasma protein and dissolve into the lipidrich brain tissue.
EYES THAT KILL
It is important to note that buprenorphine will systemically bind to lipidrich territory, specifically accumulating in areas where orbital fat is located.
Theoretically, accumulated quantities of buprenorphine stored in orbital fat, compounded in lipids over extended periods of time, could contribute to a partial loss of mobile function in the muscles responsible for modulating the optic nerve during general eye motion.
Therefore, it is possible that these compounded amounts of buprenorphine accumulated in areas rich in orbital fat, may weaken the lubricating quality of an already sensitive lipidrich neurological system.
Muscles responsible for supporting and controlling movements of the optic nerve employ this lubricating characteristic throughout all the mechanics involved in mobile function. This quality may be described as the defining characteristic of orbital fat.
Buprenorphine saturation in this lipid rich area could be causing a distortion in the supportive quality of the orbital fat at the cellular level, thus catalyzing the commonly experienced and frequently occurring migraineresembling pain associated with longterm use in patients undergoing Suboxone replacement therapy.
VISUALIZE
An aesthetically infected beauty queen, obsessed with her own image is forever transfixed in the vanity mirror. Reflections of her superiority reign supreme.
SUBOXONE SATURATION ALONG ADIPOSE ARCHITECTURE POISONING THE WISHING WELL
Coordination entities, also known as ligands, function as battery packs in the brain; operating like conductive magnetic units that complete neurological circuitry deep within cerebral tissue.
These entities are also known as ligandreceptor complexes
Both buprenorphine and ibogaine metabolites compound and affect lipid density imbedded in neural tissue. Ligands occupy each receptor for a finite period of time eventually detaching from the receptor. Relative concentrations in brain tissue and plasma are in an equilibrium. Relative concentrations leave two possible variant results. When plasma concentrations are high, mass action drives the agent into the brain. When concentrations in plasma are low, buprenorphine leeches out of the brain.
Exogenous substances such as opioid agents are excreted through the body’s defense mechanisms mainly through urine and bile at a certain rate that varies with each compound, along with micromolar (μM) amounts being eliminated through dermal pores.
Therefore, upon administering a dose of a buprenorphine, plasma levels increase in the user. During this interval of intake activity, the clearance mechanism cannot keep up with the input.
When plasma levels are high, circulation distributes the buprenorphine systemically, dissolving the agent into tissue lipids throughout the body.
Most of a given dose does not reach its intended target, but ideally, enough gets to the intended target to cause a therapeutic effect. As the clearance mechanisms eventually lower plasma concentrations, drugs are repartitioned into the bloodstream and removed from tissues.
In human pharmacology, the rate of drug clearance is expressed as “plasma halflife.” Plasma halflife refers to the amount of time it takes for the clearance mechanisms to cut the plasma concentration in half. This is measured most commonly through the comparison of serial blood tests. In general, this method is a clinically accepted diagnostic system utilized for detecting approximate levels of an agent’s binding activity at the intended receptor embedded in biological tissue.
It is possible to directly measure receptor binding in vitro by grinding up animal tissue and using sophisticated chromatography and/or radioimmunoassay tools. However, this is never done with humans. Instead, plasma halflife is compared to receptor binding kinetics in lab animals. Therefore, it is assumed that the human ratio would be about the same.
Clinical researchers currently measure plasma levels only, if measuring anything at all.
Widely circulating research articles repetitively suggest that buprenorphine will not be bound to the μopioid receptor after four to seven days following cessation of drug ingestion.
This phrasing implies that you have directly measured the μopioid receptor site’s tissue binding levels (i.e., ground and desiccated a human brain, recently in vitro/deceased).
The reality at hand is clearly much different than what the latter implies. A scientific suggestion of this
nature is hypothetically based on speculation that five plasma halflives for buprenorphine equivalates to four to seven days. This refers to the period of time it usually takes for plasma and tissue levels to go below the effective drug binding affinity, thus causing the remainder of the drug to stop working.
It should be noted, in the field of clinical research and discovery, plasma concentrations are actually a surrogate for tissue binding.
This is considered valid for single doses of any drug and for continuous dosing of watersoluble drugs. However, for the individual interested in undergoing ibogaine treatment, one should recall the fact that buprenorphine is highly lipid soluble.
Meaning, the equilibrium parameters favor partitioning of the agent into lipidic tissues rather than into plasma.
Humans have an average blood volume of five liters and an average (nonwater) tissue volume of approximately twenty liters.
If buprenorphine tends to concentrate in the tissues, which are of themselves a greater volume than the plasma, simply looking at plasma concentrations provides a significant underestimate of the actual quantity of the buprenorphine stored in the body.
Pharmacologists express this as “volume of distribution” (VoD). This signifies the amount of water
necessary if the total amounts of the drug in the body were dissolved in water at the measured plasma concentration. Buprenorphine VoD is one hundred and fifty five liters. Since psychoactive drugs must be lipid soluble to enter the brain, they all have large VoDs. For example, the VoD of highly watersoluble aspirin, is seven liters.
Due to lipid partitioning, plasma concentrations of chronicallyadministered lipid soluble drugs may significantly underestimate the total amount of the drug in the body. Due to the effects of drugs requiring the presence of a certain tissue concentrations to affect receptor binding, the possibility of underestimation is not as problematic as it may seem. Most drugs don’t bind to receptors at 1/10 or 1/100 of their effective concentrations, research can ignore the long tail of drug elimination due to lipid partitioning in most cases. However, some drugs bind to multiple receptors, each one with a different binding affinity. It might take micromolar concentrations to elicit the desired clinical effects on receptor A, but only 0.01 micromolar concentrations to activate receptor B which has either no clinical effects or may even cause adverse effects.
Therefore, it is possible that very low plasma concentrations of buprenorphine can persist for many weeks after the last dose. It takes this long for the large lipid stores to leech into the circulation and be eliminated. It is also possible that, although these concentrations are too low to give clinical benefit, they may be able
to bind to a different receptor and cause adverse effects. The majority of drugs that make it through the FDA gauntlet don’t cause adverse effects at subtherapeutic concentrations. However, if buprenorphine is combined with certain other drugs, then the combination of receptor binding patterns could possibly cause adverse effects, even at nearly invisible plasma concentrations of buprenorphine.
Results such as these could only be determined empirically, through clinical observation. The FDA requires manufacturing companies to look for drug to drug interactions between their candidate compound and a varied panel of widelyused medications. However, the FDA does not require that all possible combinations be tested before marketing. In particular, the FDA does not require testing of the interactivity of illicit or controlled compounds with their chosen drug candidates.
VISUALIZE
Ligands compound collectively, saturating designated territories like recentlyreleased renegade prisoners of war. Occupying the enemy’s capital, adrenaline fueled soldiers ravage reserves, eventually crushing the coalition’s ability to communicate clearly within the core.
MONARCHY AMONGST THE METABOLITES, SURPASSING THE PREDECESSOR PHANTOMS IN THE SHADOWS, THE EVERLASTING OPERA
Buprenorphine is extensively metabolized in humans. Excretion of the parent compound in urine is minimal.
Urine analysis is commonly relied upon when trying to detect "clean time" or drugfree time zones.
Drugfree time zones are intervals of time when a patient is considered safe from the interference effects of a recently ceased psychoactive drug, (i.e. fat soluble compounds that have been continuously ingested passed the point of reaching "steadystate" levels in plasma concentrations). Biologically,
a user of buprenorphine reaches steadystate levels at day seven.
Buprenorphine has ceiling effects with respect to analgesia and respiratory depression.
Norbuprenorphine is a dealkylated metabolite of its parent compound.
Norbuprenorphine, unlike its parent compound, is a potent opioid agonist, with high affinities for all three opioid receptors μ, κ, and δ.
As evidenced in rat tissue, norbuprenorphine functions as a full agonist
and causes full respiratory depression through rapid binding at the μreceptor.
Norbuprenorphine respiratory depression was opioidreceptor mediated, and also antagonized by buprenorphine.
Norbuprenorphine showed ten times the potency of buprenorphine.
The parent compound's major metabolite also showed respiratory depressant effects in sheep.
In humans, normal hepatic function metabolically eventuates buprenorphine into three major metabolites, norbuprenorphine, buprenorphine3glucuronide, and norbuprenorphine3glucuronide.
Clinical studies have detected plasma concentrations of the three major metabolites in humans.
Peak plasma concentrations of the three major buprenorphine
metabolites met the equivalent or exceeded those of the parent compound.
The following data presents molar area under the concentration in plasma versus time curve following a single dose of buprenorphine:
Norbuprenorphine showed 200% higher plasma concentrations than those of buprenorphine.
Buprenorphine3glucuronide showed 100%, higher plasma concentrations than those of buprenorphine.
Norbuprenorphine3glucuronide showed 600% higher plasma concentrations than those of buprenorphine.
Metabolism of buprenorphine to norbuprenorphine was originally considered to be an inactivation pathway.
An inactivation pathway can be described as the metabolic function
that renders a chemically reactive compound into an inactive compound.
Clinical evidence is now suggesting that the dealkylation of buprenorphine
to norbuprenorphine is in actuality a bioactivation pathway. A bioactivation pathway is the metabolic transformation in which a relatively inactive precursor
produces a compound that is chemically reactive.
Current status of buprenorphine glucuronide metabolites pharmacology in humans: {{{undefined}}}
VISUALIZE
A shadow personality mimics your every move. Mocking your motions like a mime artist cascading your image throughout endless halls of mirrors. There is no escaping her reflective behaviour.
Naturally, upon realizing you are no longer unique or original, you become selfconscious.
Stifling your ability to reach your objective you fail to occupy your destination point.
COMPOUNDING THROUGHOUT CAVITIES IN THE CATHEDRAL CREATIVE OCCUPYING THE ENDLESS HOURGLASS
Systemically speaking, ibogaine is a very userfriendly compound. Once transported to the liver for metabolic manipulation, the Odemethylation process initiates its catalyzation through polymorphic expression of CYP2D6. 12hydroxyibogamine, also known as noribogaine, is born out of this metabolic process of biotransformation. It has been further proposed that ibogaine is deposited into adipose tissue and then further metabolized into noribogaine following its release back into the plasma.
Clinical studies show that ibogaine does not agonize or antagonize μ and κopioid receptor sites. Noribogaine, however, showcases a binding profile with site specific differences than that of its parent compound. Clinical research studies have found that noribogaine shows higher plasma levels than ibogaine. Noribogaine is also detectable for a duration of time far exceeding the time period associated with its parent compound. Noribogaine is more potent than ibogaine in rat brain drug discrimination assays when tested for the subjective effects of ibogaine. The desmethyl metabolite may act as key equilibrium preserver, maintaining neurological harmony through its possible reassociation with the μ and κopioid receptor sites.
Clinical studies show that ibogaine binds with low micromolar μMaffinity to a multitude of molecular targets within the central nervous system, resulting in a unique complex pharmacology. The ibogaine alkaloid binds with μ and κopioid receptors, sigma2 receptors, NMDAcoupled ion channels, serotonin and dopamine transporters...The list goes on and on in regards to the parent compound’s activity. Simultaneously, noribogaine subdues opioid withdrawals at the κ and μopioid receptors. Assuming, of course, that ibogaine is properly allowed to enter adipose tissue, preserving the ability to metabolize into noribogaine through future metabolic activity.
Researchers tend to agree that the synergistic result of ibogaine and noribogaine is necessary to deliver the successful benefits associated with ibogaine treatment when employed as an opiate addiction interrupter. Researchers propose that there are many areas of the brain that may be affected by ibogaine and noribogaine that are unknown at this time. The direct biological function of ibogaine and noribogaine may continue to be a neurological mystery until empirical data can be realized. Don’t hold your breath.
What would happen if buprenorphine saturated lipidrich tissue and had reached maximum capacity through long term ligand compounding due to continuous dosing at steady state plasma levels?
How long could buprenorphine’s metabolic offspring generationally reassociate with κ and μopioid receptors once a user’s daily doses of the medication have ceased?
Would ibogaine be able to enter fatty tissue once released from the liver with buprenorphine metabolites having saturated fatty tissue at maximum capacity?
Would a Suboxone user only experience partial effects of the ibogaine experience if undergoing treatment with only having abstained from medication for a limited time prior to ibogaine therapy?
VISUALIZE
As the wartorn father walks out on his family, turning his back on the past, he disappears into the horizon, facing the setting sun.
The father’s silhouette fades smaller and smaller into the distance, all the while his youngest son grows taller and taller, in his predecessor’s shadow.
KAPPA
A LANDSCAPE EMBEDDED IN MYSTERY
A discretely located opioid receptor with the ability to modulate breathing patterns and rhythms rests awaiting activity. Controversial, in relation to the contradictory findings, regarding the differences in activity characteristics and signal pathway expression, currently remains to be completely understood.
THOUGHT
Opiate induced hypnagogia is directly or indirectly related to agonist activity at the kappa opioid receptor.
Opiate induced agonist activity at at the kappaopioid receptor site has produced oneiric visionary states, cinematic vignettes of dream sequencing as well as the more classically described fullblown hallucinogenic experiences.
Multiple κopioid receptor agonists, as well as, both the selective κopioid receptor agonists and specific κopioid receptor antagonists can produce disassociation, dysphoria, and states of hallucination in subjects undergoing clinical research and investigation.
It is possible that noribogaine agonism at the κopioid receptor is responsible for initiating the rapid eye movement activity associated with the self introspection one experiences following the ingestion of sufficient quantities of iboga extracts during what is commonly referred to as the dreamstate phase of treatment. It will likely take hundreds of clinical studies, before we truly understand the mechanisms of action responsible for determining the ibogaine alkaloid’s multitude of actions at serotonin receptors (reuptake), blockading nicotinic channels, not to mention all the rest of the action found throughout neural territory possibly responsible for catalyzing the ignition of the psychoactiveinduced state commonly referred to as the waking dream.
Hypnagogia: agōgos "leading, guiding, inducing", pompe "act of sending", hypnos “sleep”
The experience of the transitional state that spans from moment to moment wakefulness to sleep including the varying levels of lucidity encountered in between.
Hypnagogic state a self reflective state of consciousness
VISUALIZE:
At sunset, a rutilated quartz held up to the sky illuminates the eye and captivates the viewer’s attention. Each facet catches and redirects the light illuminating darkened avenues and alleyways through a subtle twist of the wrist.
Find the “phantoms,” the imperfections related to the density grading of the stone that exist throughout the central core. Find the phantoms and find the the break between clarity and chaos.
IBOGAINE & SUBOXONE RECEPTOR SITE WARFARE
Ibogaine and its desmethyl metabolite...need to exist in union within their surrounding neural environment...lipidrich territories...allowing freedom of expression....allow ibogaine and noribogaine to function in harmony......freedom from monarchy........free enterprise.
COMPETITIVE INHIBITION : Occurs when two or more drugs compete for the same enzyme.
Clinical significance of inhibition interactions rely initially on relative concentrations of the compounds involved. Specific compounds have the ability to bind and act as competitive inhibitors of different CYP enzymes. These compounds can bind both irreversibly or reversibly, inhibiting other compounds from binding enzymatically.
Mechanism based inhibition manifests when compounds are metabolized by the CYP system into active metabolites. Binding to the enzyme, these metabolites cause an irreversible loss of function.
Once this binding occurs, new activity is regained only through the synthesis of new enzymes.
Complex mechanisms of inhibition may also occur as well. Compounds undergo metabolic activation by the CYP process into inhibitory metabolites. These metabolites may generate relatively stable complexes with CYP holding cytochrome in a state of inactivity. The clinical significance to this interaction is high, due to its extensive duration of time.
Inhibition is achieved once the inhibitor reaches steady state (which is four to seven halflives), and the maximum concentration of the inhibited compound occurs once the inhibited compound reaches steady state at its new, extended halflife.
The time frame necessary to allow for the interaction to resolve itself greatly depends on halflives the compounds as well as the halflives of their active metabolites.
VISUALIZE
Strolling by a carousel spinning slowly as the evening sky loses light, you decide on a carnival ride.
Paying for a ticket, you enter an empty shadow lane.
As your chariot climbs into the darkness above, you look to your left and see that a carnival clown has hung himself...roped all the way up, swings low from the rafters. Eyes painted, little circles.
His body appears to be floating in space. Rusted hinges scrape and bounce off the rafters, echo their reflections throughout the open emptiness. Just a joke you say to yourself. A bad one. Looking down to the ground you notice that he’s sabotaged the track at top of the final drop.
A candle light left flickering in the corner, so you’d be sure to see his work one last time.
CONCLUSION
ESTABLISHING EQUILIBRIUM
Since the introduction of buprenorphine to the global market and even more so, as it is currently employed, both providers and patients alike have explored a variety of questions regarding treatment options and comparing timeline strategies in the treatment of opioid dependency post buprenorphine based replacement therapy.
How can we assure the efficacy of ibogaine therapy applied in the case of an individual that has used the buprenorphine for seven or thirteen days and contrast that with someone who employed the agent daily for twelve months continuously? Where do we start to scale the time period of abstinence needed free from buprenorphine and prior to treatment with ibogaine?
When does an individual’s lipid structure reach maximum volume?
Could continuous chemical compounding into lipid tissue reach a maximum saturation level, not allowing weaker binding ligands to enter?
Once we consider all of the relative physiological characteristics such as medication taken in relation to body weight, metabolic function of the thyroid, hepatic function of the liver, cardiac function, etc...We are left in endless speculation.
THOUGHT
Let us break the discussion down to the one core question that most greatly affects a future ibogaine patient’s outcome post Suboxone replacement therapy.
CORE QUESTION
What is the specific length of time needed for a subject to be (neurobiologically) free from exogenous doses of buprenorphine prior to undergoing ibogaine therapy in order to assure the successful application of ibogaine’s therapeutic use as an addiction interrupter?
The answer to the question above may never be collectively agreed upon due to the nature of subjectivity regarding an exact number of days, weeks or months needed. A wide span of physiological characteristics would need to be determined prior to diagnosing a former buprenorphine user, or even manipulate an individual’s time span.
One classical tactic to employ, would be to look at the anecdotal reports and simply begin by adopting the idea that some people may need a much longer time span, free of buprenorphine exogenously fed into the lipid system.
Most therapy providers are looking for an approximate timespan where one can begin to look towards the future with confidence, thus plan and treat accordingly.
If ibogaine has no function as noribogaine through normal metabolic manifestation due to its inability to enter adipose architecture, does the human body eliminate the indole alkaloid through urine intact?
How long does it take buprenorphine take to clear from the adipose tissue sufficiently so as not to disturb the beneficial results that follow ibogaine therapy?
We know that certain factions recommend a twentyone day preparation phase, others predict that a sixty or even a ninety day period of time away from buprenorphine is probably more appropriate.
All we know right now, is that no one knows.
Most ibogaine therapy practitioners tend to agree that although it may be uncommon and even rare, there are patients that have needed extensive durations of time buprenorphinefree in order to inherit the beneficial effects of ibogaine therapy following their treatment.
Patients report extended periods of post acute withdrawal symptoms persisting post ibogaine therapy sessions; some for many months following treatment.
A number of these patients return to centers for a second treatment or obtain ibogaine through internet vendors and administer themselves at a later date, after researching the residual effects of buprenorphine interfering with the efficacy of ibogaine.
Many of these questions may never be answered definitively; until empirical evidence emerges at some future date. This could obviously take a while.
Accepting this as the current reality we could simply begin by adopting a classical perspective; plant the seeds of thought leaving them open to evolve organically.
We could discard the idea of the need for empirical evidence and begin to explore the world of theoretical possibilities; continuing to discuss the possibilities that could interfere with the efficacy of ibogaine therapy.
Eventually we may notice that a further branching out of communication within our community emerges. And, rooted in confidence that the earth will provide her support, watch her take on a life of her own and bear fruit.
© Lex Kogan, 2014
RESOURCE REFERENCES
NOTE
The author of The Suboxone Papers has chosen to present the conference version of the above work free from numerical referencing (academia) in order to preserve the material’s monologic integrity.
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2005. [4] Roberts DM, & MeyerWitting M, “Highdose buprenorphine: perioperative precautions and management strategies”, Anaesth Intensive Care, 2005 Feb;33(1):1725. [5] “FDA: Subutex and Suboxone Questions and Answers”, U.S. Food and Drug Administration: Protecting Your Health”,http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm 191523.htm. [6] Cowan A, & Lewis JW, & Macfarlane IR, “Agonist and antagonist properties of buprenorphine, a new antinociceptive agent”, Br J Pharmacol, 1977 Aug;60(4):53745. [7] “Treatment Improvement Protocol (TIP) Series, No. 40“, Substance Abuse and Mental Health Service Administration, http://www.samhsa.gov/, 2004. [8]“Identification: Buprenorphine”, Drug Bank , http://www.drugbank.ca/drugs/DB00921. [9] Gower S1, & Bartu A., & I ett KF, & Doherty D., & McLaurin
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