Thursday, January 20, 2005

Sixtiesdrug moet alcoholverslaving genezen - Controversial drug shown to act on brain protein to cut alcohol use 

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Een hallucinogene drug die populair was in de jaren zestig, kan wetenschappers helpen een medische behandeling voor alcoholisme te ontwikkelen.

Dat is de conclusie van onderzoekers aan de Amerikaanse Universiteit van Californie.

De resultaten van hun onderzoek warden gepubliceerd in het Amerikaanse Journal of Neuroscience en worden nu al 'baanbrekend' genoemd.

De drug, ibogaine, is een plantenderivaat en blokt neurale verslavingsmechanismen af.
Binnen in de hersenen worden bepaalde eiwitten, die een negatief effect hebben op de (alcohol)afhankelijkheid, meer geproduceerd.
Onderzoekster Patricia Janak bevestigde dat de drug overduidelijk een positieve invloed op verslavingen heeft.
"Opiaatafhankelijke ratten die zichzelf morfine toedienen, hielden daar een voor een mee op wanneer ze ibogaine ingespoten kregen zonder date er een onthoudingssyndroom optrad. Dat deed ons besluiten dat de aan ibogaine toegeschreven effecten niet alleen psychologisch kunnen zijn, maar ook een farmacologisch karakter hebben." Anderzijds verminderden alle ratten die elke dag enkele drinkbakjes vol alcoholkregen, vrijwillig hun 'alcoholgebruik' nadat ze geinjecteerd warden met ibogaine.
Na twee weken ibogainetherapie was er een significant kleinere drang naar alcohol merkbaar bij de ratjes.


Er zijn evenwel al enkele drugs verkrijgbaar die het afkickproces zouden bevorderen, denk maar aan methanol of LSD.

Uit: De Morgen Donderdag 20 januari 2005

Controversial drug shown to act on brain protein to cut alcohol use
Public release date: 18-Jan-2005
Contact: Wallace Ravven
University of California - San Francisco

A naturally occurring hallucinogen advocated by some clinicians as a potent anti-addiction drug has been rigorously studied for the first time, confirming its ability to block alcohol craving in rodents, and clarifying how it works in the brain. The new research findings about the drug Ibogaine open the way for development of other drugs to reverse addiction without Ibogaine's side effects, potentially adding to the small arsenal of drugs that effectively combat addiction.
Derived from a West African shrub, Ibogaine has been championed for years by a cadre of clinicians and drug treatment advocates impressed with its ability to reverse withdrawal symptoms and craving for alcohol and various drugs of abuse. It has been used outside of the U.S. to treat addiction by American and other clinicians. But its side effects, including hallucinations, which made it popular in the 1960s drug culture, and evidence of toxicity to certain nerve cells in rodent studies have discouraged careful studies of its clinical potential against drug and alcohol addiction. The FDA has not approved use of Ibogaine in the U.S.

Scientists at UCSF's Ernest Gallo Clinic and Research Center have now shown definitively in experiments with mice and rats that Ibogaine does reduce alcohol consumption, and they have determined that it does so by increasing the level of a brain protein known as glial cell line-derived neurotrophic factor, or GDNF. In a separate study, they demonstrated that GDNF by itself decreases alcohol consumption.

The research is being published in the January 19 issue of The Journal of Neuroscience.

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Ketamine Induces Dopamine-Dependent Depression of Evoked Hippocampal Activity in...Hunt et al. J. Neurosci..2005; 25: 524-531.


1960s drug 'alcoholism cure hope'

Comparison of Mesocorticolimbic Neuronal Responses During Cocaine and Heroin Self-Administration in Freely Moving Rats

Jing-Yu Chang, Patricia H. Janak, and Donald J. Woodward

Department of Physiology and Pharmacology, Wake Forest University, School of Medicine, Winston-Salem, North Carolina 27157

To compare neuronal activity within the mesocorticolimbic circuit during the self-administration of cocaine and heroin, multiple-channel single-unit recordings of spike activity within the rat medial prefrontal cortex (mPFC) and nucleus accumbens (NAc) were obtained during the consecutive self-administration of cocaine and heroin within the same session. The variety of neuronal responses observed before the lever press are termed anticipatory responses, and those observed after the lever press are called post-drug infusion responses. For the total of the 110 mPFC and 111 NAc neurons recorded, 30-50% of neurons, depending on the individual sessions, had no alteration in spike activity in relation to either cocaine or heroin self-administration. Among the neurons exhibiting significant neuronal responses during a self-administration session, only a small portion (16-25%) of neurons responded similarly under both reinforcement conditions; the majority of neurons (75-84%) responded differently to cocaine and heroin self-administration as revealed by variations in both anticipatory and/or post-drug infusion responses. A detailed video analysis of specific movements to obtain the self-administration of both drugs provided evidence against the possibility that locomotive differences contributed to the observed differences in anticipatory responses. The overall mean activity of neurons recorded in mPFC and NAc measured across the duration of the session segment for either cocaine or heroin self-administration also was different for some neurons under the two reinforcement conditions. This study provides direct evidence that, in mPFC and NAc, heterogeneous neuronal circuits mediate cocaine and heroin self-administration and that distinct, but overlapping, subpopulations of neurons in these areas become active during operant responding for different reinforcers.
Key words: electrophysiology; cocaine; heroin; mesocorticolimbic system; medial prefrontal cortex; nucleus accumbens; reinforcement; reward; drug abuse; behavior


Confirmed: Hallucinogen Fights Addiction
Ibogaine reduces alcohol consumption and increases addiction-fighting brain protein

Betterhumans Staff
1/18/2005 7:40 PM

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Credit: TheD
Breaking the cycle:

The hallucinogen ibogaine activates a
brain protein that blocks increased
alcohol craving and consumption
following periods of abstinence

A hallucinogen advocated as a potent anti-addiction drug has received support from research showing that it can block alcohol cravings in rodents by boosting an addiction-fighting brain protein.
The drug, ibogaine, is derived from a West African shrub called Tabernanthe iboga. For years it has attracted attention for its ability to reverse withdrawal symptoms and cravings for alcohol and other addictive substances.
Used outside the US to treat addiction, it is not approved in the country by the Food and Drug Administration. Side-effects such as hallucinations, which made it a popular recreational drug in the 1960s, have impeded clinical studies of its addiction-fighting capabilities.
American researchers at the University of California, San Francisco have now shown in mice and rats that the drug reduces alcohol consumption, and that it does so by increasing levels of the brain protein glial cell line-derived neurotrophic factor (GDNF). The researchers have also shown that GDNF alone decreases alcohol consumption.
"By identifying the brain protein that ibogaine regulates to reduce alcohol consumption in rats, we have established a link between GDNF and reversal of addiction—knowledge of a molecular mechanism that should allow development of a new class of drugs to treat addiction without ibogaine's side-effects," says study coauthor Dorit Ron.
New treatments possible
For their research, Ron and colleagues first gave rats alcohol until they became daily drinkers. They then withdrew alcohol for two weeks, which is known to greatly increase drinking when alcohol becomes available again.
Administering ibogaine, however, significantly reduced the heightened craving and consumption. The drug was given by injection or directly into the brain. Rats receiving it drank less and were less likely to fall off the wagon and revert to their previous drinking habits.
"The discovery that Ibogaine reduced binge drinking after a period of abstinence was an exciting finding for us because this is the type of behavior in alcoholics for which very few effective drugs exist," says study coauthor Patricia Janak.
The researchers also confirmed in a cell model that ibogaine stimulated GDNF activity. They then confirmed that this was responsible for the drug's anti-addiction effects by using a GDNF inhibitor in the rats. This blocked ibogaine's ability to decrease alcohol craving.
"If we can alter the GDNF pathway, we may well have a new treatment against alcohol and drug addiction without the unwanted side-effects of Ibogaine," says Ron.
The research is reported in The Journal of Neuroscience.


Signal transduction, Molecular Neurobiology of Addiction

Research Summary

The lab's main interest is in the molecular mechanisms underlying synaptic plasticity, and addiction. We use molecular biology, molecular pharmacology, and electrophysiology in parallel with behavioral models to study how scaffolding proteins and signaling complexes regulate neuronal functions such as that of the NMDA receptor, the growth factors BDNF and GDNF, and neuronal gene expression. We then study how these normal processes are altered in the presence of acute or long-term exposure to ethanol, and how these lead to either the development or the prevention of alcohol addiction. Understanding how ethanol changes signaling cascades has and will continue to identify new potential drug targets.


Interessant.Ibogaine wordt in Nederland al zo'n zestal jaar onderzocht maar de researchers moeten met een te klein budget werken,na het fiasco van de heer ... (naam ontschiet mij),die probeerde P.T.T.S. te genezen bij voormalige concentratiekampgevangenen met gebruik van L.S.D. 25.En due to de econ.cris. zijn alle budgetten sowieso ingekrompen...
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