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Harmalin och harmin mot drogberoende
har likheter med ibogain
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Masque
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PostPosted: Sat 05 Jan, 2008 12:03    Post subject: Harmalin och harmin mot drogberoende Reply with quote

Jag satt och studerade ett patent av Howard lotsof och såg följande:

Quote:

Method of treating chemical dependency using b-carboline alkaloids

EXAMPLE 1

Subjects were male Long Evans rats, weighing 175-200 grams at start. Rats were housed in individual cages in a temperature controlled room. They were kept on a 12:12 hour, light:dark cycle. Food and water were continuously available.

After four days of acclimatization to the animal room, rats were given a 2 percent solution of ethanol in a free choice paradigm with water. Water and ethanol were presented in Richter tubes mounted on the front of each cage. The next day, water only was given in the two tubes. The third day, the positions of the tubes were reversed and the concentration of ethanol was increased by 1 percent. This alternate day and alternate side exposure was repeated until a concentration of 10 percent ethanol was reached. The rats were then presented with a 10 percent ethanol solution for seven consecutive days. Tube position reversal was continued during this seven day period.

Harmaline HCl was dissolved in distilled water to a concentration of 8 mg/ml. Animals were divided into three groups receiving either saline, 20 mg/kg or 40 mg/kg of harmaline on alternate days.

Interperitoneal harmaline and saline administrations were carried out over a period of nine days on days one, three, five, seven and nine. The 40 mg/kg harmaline group consistently demonstrated a reduction of approximately two thirds that of the control group's ethanol consumption both during the treatment period and the ten day post treatment period.

EXAMPLE 2

A second experiment was conducted using a 10 mg/kg dose of harmaline administered interperitoneally on a daily basis for five days. Similar results were observed. The treated group showed ethanol consumption ranging from one half to one quarter that of control group during the five days of daily harmaline administration. The five day post treatment period showed the harmaline group drinking fifty to twenty five percent less ethanol than the control group.

Additional research showed harmine to produce similar physiological effects as harmaline at approximately 400 percent the dose of harmaline.

EXAMPLE 3

A twenty-three year old, 140 pound male human subject using one to three grams of cocaine daily via nasal administration was provided a single dose of 500 mg of harmaline HCl per os. Subject immediately discontinued cocaine use. Subject's cocaine use was interrupted for a period of four months. Subject had been previously treated with 500 mg of a total alkaloid extract of T. iboga with no significant effect on drug use. Conversely, it should be noted, however, that three persons successfully treated with ibogaine had no response to the administration of harmaline in interrupting their drug use.

EXAMPLE 4

A thirty-two year old, 136 pound male human subject using twenty dollars worth of heroin a day (approximately 40 mg/day) via IV route. The subject interspersed his use of heroin with 15 mg and 30 mg injections of morphine and unknown quantities of pantopon. The subject was given an IV injection of 100 mg of harmaline HCl. A second 100 mg IV injection of harmaline HCl was given six hours later. Subject discontinued heroin use for a period of three weeks after which contact with the subject was lost. Subject's cigarette consumption which had been between one and two packs a day immediately ceased. This continued for ten days after which subject began smoking at a reduced rate. It should be noted that IV administrations of harmala alkaloids are significantly more toxic than oral administrations and it is advised that they not be used in medical practice.

EXAMPLE 5

Male subject, twenty-four years of age, weighing 153 pounds was using 20 mg of heroin and 250 mg of cocaine per day both via IV route and was drinking twelve to sixteen cups of coffee per day. Subject was administered 750 mg of harmaline base in a split dose of 500 mg followed by 250 mg twenty minutes later. Subject's use of heroin and cocaine ceased immediately. Coffee consumption initially dropped to one half to one cup per day but, was increased to three to four cups per day within two weeks. Cocaine use ceased for a period of two months at which time subject began nasal use of approximately 50 mg/day. Within three months subject was using cocaine and amphetamine IV and barbiturates per os. Subject had not returned to heroin use at this time but, contact with the subject was lost and no further information was available.

EXAMPLE 6

Male subject, age twenty-two, estimated weight 120 pounds, using two grams of amphetamine and/or desoxyephedrine per day via IV route was administered 500 mg of harmaline base. Subject immediately ceased stimulant use. Contact was lost two weeks later when subject left city in which treatment was administered for location unknown.

The present invention, thus, affords an effective means of treating a chemical dependency disorder, an abuse syndrome or a combination thereof. The effectiveness thereof is evidenced by either a reduced or interrupted intake of substances tending to cause the disorder or syndrome. Thus, as described hereinabove, the treatment of the present invention leads to either a reduced or interrupted intake of such substances by the subject mammal. Further, this result may be obtained without generating a subsequent chemical dependency disorder or abuse syndrome based upon the treatment.

Having described the present invention, it will be apparent to one of ordinary skill in the art that many changes and modifications may be made to the embodiments described above without departing from the spirit and scope of the present invention.


Källa: http://www.freepatentsonline.com/5591738.html


Att harmalaalkaloiderna kunde användas på detta sättet var för mig en nyhet. jag kände ju till att de är MAO-hämmare och används som medicin och hallucinogen av indianer i Sydamerika, men inte att de påverkar opiat och kokainberoende på sättet som nyss redovisades. Mycket intressant!


OBS! Nu uppmanar jag ingen att börja injicera extrakt av Peganum harmala eller liknande, gör inte det, det kan äventyra din hälsa.


Harmalin och harmin är till skillnad från ibogain inte narkotikaklassat i Sverige och tillgången är mycket högre eftersom frön från P. harmala används för bl.a tygfärgning i Mellan östern och innehåller 2-7% harmalin och harmin.... priset för en dos skulle kunna hamna under 20kr.

Är det någon som kan gräva fram mer information om forskning om harmalin och/eller harmin mot drogberoende?

Det finns något här, men jag kan inte läsa hela:

Quote:
The effects of β-carbolines in rats trained with ibogaine as a discriminative stimulus

The structural features and hallucinogenic properties shared by ibogaine and certain β-carbolines prompted the evaluation of several representative β-carbolines in rats trained with ibogaine as a discriminative stimulus. In a previous report from our laboratory harmaline completely substituted for ibogaine (83.5%). In the present study, only 6-methoxyharmalan completely substituted (86.3%). However, partial substitution was observed with harmine, harmane, harmalol, and tetrahydro-β-carboline (THBC). Norharmane and 6,7-dimethoxy-4-ethyl–carboline-3-carboxylate (DMCM) failed to produce appreciable substitution. These results provide evidence for an ibogaine-like effect of certain β-carbolines. Whether this extends to the previously reported anti-addictive effects of ibogaine remains to be established.

Källa


Last edited by Masque on Fri 28 Mar, 2008 20:46; edited 3 times in total
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Masque
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PostPosted: Sat 05 Jan, 2008 12:34    Post subject: Reply with quote

Hittade några till:

Quote:
Effects of harman and harmine on naloxone-precipitated withdrawal syndrome in morphine-dependent rats

The effects of the beta-carbolines, harman and harmine, on naloxone-precipitated withdrawal syndrome in morphine-dependent rats were investigated. Two morphine pellets containing 75 mg morphine base were implanted subcutaneously in the scapular area of adult male Wistar rats (200–250 g) under light ether anesthesia. Rats were then assigned to several groups (n = 12 for each group). Seventy-two hours after morphine implantation, harman (5 and 10 mg/kg), harmine (5 and 10 mg/kg) or saline was injected to rats intraperitoneally (ip). After 45 min, a morphine withdrawal syndrome was precipitated by naloxone (2 mg/kg, ip), and morphine withdrawal signs were observed and evaluated for 15 min. Harmine (5 and 10 mg/kg) attenuated significantly the intensity of all signs of morphine withdrawal except for jumping. While jumping behaviour appearing in morphine withdrawal was intensified by harman (5 and 10 mg/kg) treatment, harmine administration did not produce any significant change in the intensity of this sign. Harman attenuated significantly the intensity of wet dog shakes, writhing, defecation, tremor and ptosis. However, it produced no significant changes in the intensity of teeth chattering and diarrhea. Our results suggest that harman and harmine, ß-carbolines, have some beneficial effects on naloxone-precipitated morphine withdrawal syndrome in rats. Findings from the present study also indicated that harmine was more effective than harman on morphine abstinence syndrome.

Källa


Quote:
Inhibitory Effect of Harmane on Morphine-Dependent Guinea Pig Ileum

Studies on the occurrence and properties of b-carbolines structurally related to harmala alkaloids have gained attention since it was hypothesized that some of these compounds play a role in processes of substance abuse and dependence. This study investigates the effects of harmane on naloxone-precipitated withdrawal syndrome in morphine-dependent guinea pig ileum. Segments of ilea from starved male guinea pigs were obtained and fixed at a resting tension of 1 g in an organ bath containing 1026 M morphine in Tyrode solution at 378C, which was bubbled with 95% O2 and 5% CO2. Tissues were incubated in 1026 M morphine containing Tyrode solution for 4 hours before harmane was added. Naloxone and harmane had no effect on naive ilea. Naloxone (1026 M) contracted morphine-dependent ilea. Harmane significantly inhibited the contractile response to naloxone in a dose-dependent manner (1027 M 5 24%; 1026 M 5 49.3%; 1025 M 5 70%). These results suggest that harmane may have beneficial effects on morphine withdrawal syndrome.

Källa: http://www.annalsnyas.org/cgi/content/abstract/1009/1/185


Quote:
Norharman and alcohol-dependency in male Wistar rats

We examined the effects of ethanol ingestion to rats on levels of the ß-carboline norharman in plasma, brain and liver at the end of ethanol ingestion and 10 h after withdrawal. We also investigated the effect of exogenously administered norharman on the behavioural signs of alcohol withdrawal. Ethanol was given by a liquid diet for 21 days. Norharman plasma levels in alcohol fed rats were significantly elevated compared to both control rats and to rats 10 h after withdrawal. Norharman levels in brains and livers showed a similar pattern. The capacity of the livers of both alcohol-dependent and withdrawal rats to catabolise norharman was significantly reduced compared to control rats. Norharman injected intraperitoneally (6.3 mg/kg) attenuated the behavioural signs of alcohol withdrawal significantly. The mechanism behind the increased norharman levels in alcohol-dependent rats may be inhibition of the synthesis and/or activity of liver enzyme(s) responsible for the breakdown of norharman.

Källa
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Masque
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PostPosted: Fri 11 Jan, 2008 23:03    Post subject: Reply with quote

Quote:
At the very end of October David Goldstein showed up at 9 Bleecker with important news: a researcher named Poppik* had discovered Ibogaine activity at the same NMDA (N-Methy-D-Aspartate) receptor as harmaline (Woods, 1982).

Popik characterized Ibogaine and its cogeners including harmaline as "noncompetitive" NMDA antagonists [binding only one micron more to the NMDA receptor, according to Molliver, than to the kappa opiate receptor]. In effect they are more like nor-harman, the neuro-transmitter associated with REM, eidetic memory and the NDE, as opposed to serotonergic indole ring alkaloids like LSD.

In David's materials on the NMDA receptor were papers on the potent anti-stroke medication diszolcilpine (MK801). Both Ibogaine and harmaline displace the somewhat oneiric MK801, suggesting a common mechanism of action. Daily administration of MK801 attenuated both tolerance to and dependence upon alcohol and morphine.*** Also, MK 801 has been also found to inhibit the supersensitization to cocaine that sometimes occurs with tolereance to cocaine.**

MK 801 is a hallucinogen -- more related to phencyclidine and ketamine than Ibogaine/harmaline. Yet FDA approved it, because an injection of MK801, even half an hour after a stroke, by blocking flow of potassium, sodium and calcium ions into brain cells, interferes with the normal "glutamate cascade" that fuels neurologic stroke damage, cutting it 50 to 75%.


http://www.cures-not-wars.org/ibogaine/chap18.html
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Masque
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PostPosted: Tue 15 Jan, 2008 21:41    Post subject: Reply with quote

Hittade en till.

Ni måste hålla med om att det här är mycket intressant? Kommentarer någon?
Är det någon som har access till dom här pdf:erna och kan lägga upp dom på något ställe där vi kan hämta hem dom?

Quote:

High-affinity binding of β-carbolines to imidazoline I2B receptors and MAO-A in rat tissues: Norharman blocks the effect of morphine withdrawal on DOPA/noradrenaline synthesis in the brain

This study was designed to determine the affinity and binding profile of β-carbolines for imidazoline I2 receptors and catalytic sites of monoamine oxidase (MAO)-A/B in rat brain and liver. The aim was also directed to assess the in vivo effects of norharman (β-carboline) and LSL 60101 (I2 ligand) on brain 3,4-dihydroxyphenylalanine (DOPA) synthesis in morphine-dependent rats. Competition experiments against [3H]2-BFI revealed that β-carbolines recognize the high- and low-affinity components of the brain imidazoline I2 receptor with the rank order of potency (KiH in nM): noreleagnine (12) > norharman (20) > harmalol (82) > harmaline (177) much greater-than harmine (630) > harman (700) much greater-than FG-7142 (> 100,000). In liver, this rank was different: harmine (51) > harmaline (103) = noreleagnine (103) much greater-than harmalol (1290) > harman (2000) much greater-than norharman (12,382) much greater-than FG-7142 (> 100,000). In brain and liver, competition curves for β-carbolines against [3H]Ro41-1049 (MAO-A) and [3H]Ro19-6327 (MAO-B) were monophasic and resulted in different drug potencies for the two MAO isozymes (higher affinities for MAO-A) and in similar pharmacological profiles in both tissues. In morphine-dependent rats, naloxone (2 mg/kg, 2 h)-precipitated withdrawal increased the synthesis of DOPA in the cerebral cortex and hippocampus (50%). Pretreatment with norharman (20 mg/kg) or LSL 60101 (20 mg/kg) (30 min before naloxone) fully prevented the stimulatory effect of opiate withdrawal on DOPA synthesis. Norharman and LSL 60101 also attenuated the severity of the withdrawal syndrome. The results indicate that β-carbolines bind with high affinity to imidazoline I2B receptors, and similarly to I2 ligands (LSL 60101) can block the behavioural and biochemical effects of opiate withdrawal.

Källa

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