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Ibogaine – Binding profile

Ibogaine has affinity (Ki) for the following sites in decreasing order of potency: σ2 (206 nM) > SERT (548.7 nM) > DAT (1,980 nM) > NMDA (2,001 nM) > κ-opioid (2,717 nM) > µ-opioid (4,362 nM) > σ1 (5,839 nM) > M3 (12,500 nM) > 5-HT2A (14,142 nM) > M1 (22,486 nM) > M2 (39,409 nM) > D3 (70,000 nM).[42] It also has affinity for VMAT and the nACh receptors, among other targets
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Ibogaine – Metabolites

Ibogaine is metabolized in the human body by cytochrome P450 2D6, and the major metabolite is noribogaine (12-hydroxyibogamine). Noribogaine is most potent as a serotonin reuptake inhibitor and acts as a moderate κ- and weak µ-opioid receptor full agonist and therefore, also has an aspect of an opiate replacement similar to compounds like methadone. It is possible that this action of noribogaine at the kappa opioid receptor may indeed contribute significantly to the psychoactive effects attributed to ibogaine ingestion; salvia divinorum, another plant recognized for its strong hallucinogenic properties, contains the chemical salvinorin-A which is a highly selective kappa opioid agonist. Both ibogaine and noribogaine have a plasma half-life of around two hours in the rat, although the half-life of noribogaine is slightly longer than the parent compound. It is proposed that ibogaine is deposited in fat and metabolized into noribogaine as it is released.Noribogaine shows higher plasma levels than ibogaine and may therefore be detected for longer periods of time than ibogaine. Noribogaine is also more potent than ibogaine in rat drug discrimination assays when tested for the subjective effects of ibogaine. The Noribogaine differs from ibogaine in that it contains a hydroxy instead of a methoxy group at the 12 position

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Ibogaine – Pharmacology

The pharmacology of ibogaine is quite complex, affecting many different neurotransmitter systems simultaneously.Because of its fairly low potency at any of its target sites, ibogaine is used in doses anywhere from 5 mg/kg of body weight for a minor effect to 30 mg/kg in the cases of strong polysubstance addiction. It is unknown whether doses greater than 30 mg/kg in humans produce effects that are therapeutically beneficial, medically risky, or simply prolonged in duration. In animal neurotoxicity studies, there was no observable neurotoxicity of ibogaine at 25 mg/kg, but at 50 mg/kg, one-third of the rats had developed patches of neurodegeneration, and at doses of 75 mg/kg or above, all rats showed a characteristic pattern of degeneration of Purkinje neurons, mainly in the cerebellum. While caution should be exercised when extrapolating animal studies to humans, these results suggest that neurotoxicity of ibogaine is likely to be minimal when ibogaine is used in the 10–20 mg/kg range typical of drug addiction interruption treatment regimes, and indeed death from the other pharmacological actions of the alkaloids is likely to occur by the time the dose is high enough to produce consistent neurotoxic changes.

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Ibogaine – In popular culture

Ibogaine first appeared in popular culture in the writings of Hunter S. Thompson. While covering the Wisconsin primaries of the 1972 U.S. Presidential primaries for Rolling Stone magazine, Thompson claimed that presidential candidate Edmund Muskie showed symptoms of being under the influence of Ibogaine. This assertion was later revealed by Thompson to be false, one that he had planted as media bait. He himself was surprised when the leading media outlets picked up the story and ran with it.

It also appeared in the seventh episode of the eleventh season of Law & Order: Special Victims Unit. In the episode, Doctor Huang administers Ibogaine to a heroin addict so that he can testify against a murderer

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Ibogaine – Research

An ibogaine research project was funded by the US National Institute on Drug Abuse in the early 1990s. The National Institute on Drug Abuse (NIDA) abandoned efforts to continue this project into clinical studies in 1995, citing other reports that suggested a risk of brain damage with extremely high doses and fatal heart arrhythmia in patients having a history of health problems,[citation needed] as well as inadequate funding for ibogaine development within their budget. However, NIDA funding for ibogaine research continues in indirect grants often cited in peer-reviewed ibogaine publications.

In addition, after years of work and a number of significant changes to the original protocol, on August 17, 2006, a MAPS-sponsored research team received “unconditional approval” from a Canadian Institutional Review Board (IRB) to proceed with a long-term observational case study that will examine changes in substance use in 20 consecutive people seeking ibogaine-based therapy for opiate dependence at the Iboga Therapy House in British Columbia, Canada.

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Ibogaine – Legal status

Ibogaine and its salts were regulated by the U.S. Food and Drug Administration in 1967 pursuant to its enhanced authority to regulate stimulants, depressants, and hallucinogens granted by the 1965 Drug Abuse Control Amendments (DACA) to the Federal Food, Drug, and Cosmetic Act. In 1970, with the passage of the Controlled Substances Act, it was classified as a Schedule I-controlled substance in the United States, along with other psychedelics such as DMT and mescaline. Since that time, several other countries, including Sweden, Denmark, Belgium, and Switzerland, have also banned the sale and possession of ibogaine. Although illegal in these countries, ibogaine has been used by hundreds of drug dependents in the United States and abroad. Howard Lotsof, a pioneer in bringing awareness to ibogaine’s success in helping hardcore drug dependents to quit their addiction, and others have been offering willing persons the treatment. In the Czech Republic and Slovenia, taking advantage of less prohibitive legal systems, ibogaine has been applied to people coming from the U.S. and other countries seeking a safe haven.

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Ibogaine – Psychoactive effects

At doses of around 3–5 mg/kg of body weight, ibogaine has a mild stimulant effect. The high-dose ibogaine experience of 10 mg/kg or greater most commonly occurs as two distinct phases: the visual phase and the introspective phase

The visual phase is characterized by open-eye visuals, closed-eye visuals, and dreamlike sequences. Objects may be seen as distorted, projecting tracers, or having moving colors or textures. When the eyes are closed, extremely detailed and vivid geometric and fractal visions may be seen. Subjective reports often include a movie-like recollection of earlier life experiences as well as dreamlike sequences with symbolism of one’s present or anticipated future. Other effects in the visionary phase may include laughing, sensations of euphoria or fear, and temporary short-term memory impairment. The visionary phase usually ends after one to four hours, after which the introspective phase begins.

The introspective phase is typically reported to bring elevated mood, a sense of calm and euphoria, and a distinct intellectual and emotional clarity. Subjects often report being able to accomplish deep emotional and intellectual introspection into psychological and emotional concerns. It is also during this period that opioid addicts first notice the absence of withdrawal symptoms or cravings. The duration of the introspective phase is highly variable, usually lasting hours but sometimes lasting days.

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Drug

Drug

Coffee is the most widely used psychoactive drug beverage in the world. In 1999 the average consumption of coffee was 3.5 cups per day per U.S. citizen.

Wine is a common alcoholic beverage.

A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function.There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.

In pharmacology, a drug is “a chemical substance used in the treatment, cure, prevention, or diagnosis of disease or used to otherwise enhance physical or mental well-being.”Drugs may be prescribed for a limited duration, or on a regular basis for chronic disorders.

Recreational drugs are chemical substances that affect the central nervous system, such as opioids or hallucinogens. They may be used for perceived beneficial effects on perception, consciousness, personality, and behavior. Some drugs can cause addiction and/or habituation.

Drugs are usually distinguished from endogenous biochemicals by being introduced from outside the organism.[citation needed] For example, insulin is a hormone that is synthesized in the body; it is called a hormone when it is synthesized by the pancreas inside the body, but if it is introduced into the body from outside, it is called a drug. Many natural substances such as beers, wines, and some mushrooms, blur the line between food and recreational drugs, as when ingested they affect the functioning of both mind and body and some substances normally considered drugs such as DMT (Dimethyltryptamine) are actually produced by the human body in trace amounts.

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Etymology

Drug is thought to originate from Old French “drogue”, possibly deriving later into “droge-vate” from Middle Dutch meaning “dry barrels”, referring to medicinal plants preserved in them.

Medication

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A medication or medicine is a drug taken to cure and/or ameliorate any symptoms of an illness or medical condition, or may be used as preventive medicine that has future benefits but does not treat any existing or pre-existing diseases or symptoms.

Dispensing of medication is often regulated by governments into three categories—over-the-counter (OTC) medications, which are available in pharmacies and supermarkets without special restrictions, behind-the-counter (BTC), which are dispensed by a pharmacist without needing a doctor’s prescription, and Prescription only medicines (POM), which must be prescribed by a licensed medical professional, usually a physician.[citation needed]

In the United Kingdom, BTC medicines are called pharmacy medicines which can only be sold in registered pharmacies, by or under the supervision of a pharmacist. These medications are designated by the letter P on the label.[8] The range of medicines available without a prescription varies from country to country.

Medications are typically produced by pharmaceutical companies and are often patented to give the developer exclusive rights to produce them, but they can also be derived from naturally occurring substance in plants called herbal medicine.[citation needed] Those that are not patented (or with expired patents) are called generic drugs since they can be produced by other companies without restrictions or licenses from the patent holder.

Spiritual and religious use

The spiritual and religious use of drugs has been occurring since the dawn of our species. Drugs that are considered to have spiritual or religious use are called entheogens. Some religions are based completely on the use of certain drugs. Entheogens are mostly hallucinogens, being either psychedelics or deliriants, but some are also stimulants and sedatives.

Self Improvement

Nootropics, also commonly referred to as “smart drugs”, are drugs that are claimed to improve human cognitive abilities. Nootropics are used to improve memory, concentration, thought, mood, learning, and many other things. Some nootropics are now beginning to be used to treat certain diseases such as attention-deficit hyperactivity disorder, Parkinson’s disease, and Alzheimer’s disease. They are also commonly used to regain brain function lost during aging. Similarly, Drugs such as steroids improve human physical capabilities and are sometimes used (legally or not) for this purpose, often by professional athletes.

Recreational drug use

The cigarette is the common pharmaceutical form of tobacco – one of the world’s best selling drugs.

Cannabis is another commonly used recreational

drug

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Recreational drugs use is the use of psychoactive substances to have fun, for the experience, or to enhance an already positive experience. National laws prohibit the use of many different recreational drugs and medicinal drugs that have the potential for recreational use are heavily regulated. Many other recreational drugs on the other hand are legal, widely culturally accepted, and at the most have an age restriction on using and/or purchasing them. These include alcohol, tobacco, betel nut, and caffeine products in the west, and in other localised areas of the world drugs such as Khat are common. Because of it’s the legal status of many drugs, recreational drug use is controversial; with many governments not recognising spiritual or other perceived uses for drugs and classing them under illegal recreational use.

Administering drugs

Drugs, both medicinal and recreational, can be administered in a number of ways. Many drugs can be administered in a variety of ways rather than just one.

  • Bolus
  • Inhaled, (breathed into the lungs), as an aerosol or dry powder. (This includes smoking a substance)
  • Injected as a solution, suspension or emulsion either: intramuscular, intravenous, intraperitoneal, intraosseous.
  • Insufflation, or snorted into the nose.
  • Orally, as a liquid or solid, that is absorbed through the intestines.
  • Rectally as a suppository, that is absorbed by the rectum or colon.
  • Sublingually, diffusing into the blood through tissues under the tongue.
  • Topically, usually as a cream or ointment. A drug administered in this manner may be given to act locally or systemically.
  • Vaginally as a suppository, primarily to treat vaginal infections.

Legal definition of drugs

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Some governments define the term drug by law. In the United States, the Federal Food, Drug, and Cosmetic Act definition of “drug” includes “articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals” and “articles (other than food) intended to affect the structure or any function of the body of man or other animals.”Consistent with that definition, the U.S. separately defines narcotic drugs and controlled substances, which may include non-drugs, and explicitly excludes tobacco, caffeine and alcoholic beverages. Drug

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Ibogaine – Pharmacodynamics

Among recent proposals for ibogaine mechanisms of action is activation of the glial cell line-derived neurotrophic factor (GDNF) pathway in the ventral tegmental area (VTA) of the brain. The work has principally been accomplished in preclinical ethanol research, where 40 mg/kg of ibogaine caused increases of RNA expression of GDNF in keeping with reduction of ethanol intake in the rat, absent neurotoxicity or cell death.[34]

Ibogaine is a noncompetitive antagonist at α3β4 nicotinic receptors, binding with moderate affinity.[35] Several other α3β4 antagonists are known, and some of these, such as bupropion (Wellbutrin or Zyban), and mecamylamine, have been used for treating nicotine addiction. This α3β4 antagonism correlates quite well with the observed effect of interrupting addiction. Co-administration of ibogaine with other α3β4 antagonists such as 18-MC, dextromethorphan or mecamylamine had a stronger anti-addictive effect than when it was administered alone.[36] Since α3β4 channels and NMDA channels are related to each other and their binding sites within the lumen bind a range of same ligands (e.g. DXM, PCP),[37] some older sources suggested that ibogaine’s anti-addictive properties may be (partly) due to it being an NMDA receptor antagonist.[38] However, ligands, like 18-MC, selective for α3β4- vs. NMDA-channels showed no drop-off in activity.

It is suspected that ibogaine’s actions on the opioid and glutamatergic systems are also involved in its anti-addictive effects. Persons treated with ibogaine report a cessation of opioid withdrawal signs generally within an hour of administration.

Ibogaine is a weak 5HT2A receptor agonist, and although it is unclear how significant this action is for the anti-addictive effects of ibogaine, it is likely to be important for the hallucinogenic effects. Ibogaine is also a sigma2 receptor agonist.

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Ibogaine – Formulations

In Bwiti religious ceremonies, the rootbark is pulverized and swallowed in large amounts to produce intense psychoactive effects. In Africa, iboga rootbark is sometimes chewed, which releases small amounts of ibogaine to produce a stimulant effect. Ibogaine is also available in a total alkaloid extract of the Tabernanthe iboga plant, which also contains all the other iboga alkaloids and thus has only about one-fifth the potency by weight as standardized ibogaine hydrochloride.

Total alkaloid extracts of T. iboga are often loosely called “Indra extract”. However, that name actually refers to a particular stock of total alkaloid extract produced in Europe in 1981. The fate of that original stock (as well as its original quality) is unknown.

Currently, pure crystalline ibogaine hydrochloride is the most standardized formulation. It is typically produced by the semi-synthesis from voacangine in commercial laboratories. Ibogaine has two separate chiral centers which means that there a four different stereoisomers of ibogaine. These four isomers are difficult to resolve.

A synthetic derivative of ibogaine, 18-methoxycoronaridine (18-MC), is a selective α3β4 antagonist that was developed collaboratively by the neurologist Stanley D. Glick (Albany) and the chemist Martin E. Kuehne (Vermont). This discovery was stimulated by earlier studies on other naturally occurring analogues of ibogaine such as coronaridine and voacangine that showed these compounds also have anti-addictive properties.

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