Ibogaine and Addiction

Can a psychedelic shrub diminish drug cravings?

In 1957, two scientists in the research department of CIBA Pharmaceutical Products in New Jersey reported on “an indole alkaloid with central-stimulant properties” used by native peoples in the Congo: “The crude extracts of Tabernanthe iboga caused a feeling of excitement, drunkenness, mental confusion, and, possibly, hallucinations.” The CIBA researchers were working from early reports by French and Belgian explorers in the 1800s, which had noted the use of this remarkable shrub in the Congo and surrounding regions.

Years later, a few researchers had begun to wonder whether ibogaine might not harbor properties that could be used in psychiatry and the treatment of addiction. It was the beginning of an unlikely renaissance in the study of psychedelic drugs.

A little-noticed article in the journal Brain Research in 1994 detailed the results of work with ibogaine at Albany Medical College in New York. Certain mysterious alkaloids—ibogaine in particular—decreased the self-administration of cocaine in rats--presumably through effects on the “dopaminergic mesolimbic system.” It was later determined that ibogaine also exhibited a weak affinity for one of the less common opiate sites, the kappa opiate receptor.

The active ingredient in ibogaine does not produce a classic psychedelic high, even at peak dosages. It is a state more like waking REM sleep, accompanied by hypnagogic images. Some users feel nothing at all, except intense nausea, palsy, and the sound of rushing water in their ears.

In an unexpected return to the psychedelic solution, an odd assortment of ex-hippies, AIDS activists, addiction treatment experts, and maverick scientists fell in behind the use of the African plant drug as a powerful agent for “addiction interruption.” Ibogaine, a drug that Hunter S. Thompson made famous when he joked that it might have been responsible for the downfall of Edmund Muskie’s 1972 presidential campaign, has been cited by some scientists for its ability to free certain cocaine and heroin addicts from their cravings. Initial underground experimentation was aimed at heroin addicts, but the hallucinogenic plant was also tried on alcoholics, cigarette smokers, and cocaine addicts. (The unlikely saga of ibogaine is related in The Ibogaine Story, self-published by Paul De Rienzo and Dana Beal).

Recently, ibogaine gained renewed attention in the usual way—by attenuating alcohol intake in various strains of alcohol-preferring rats. In the January 19 issue of The Journal of Neuroscience, researchers at the University of California-San Francisco (UCSF) reported that ibogaine substantially decreased alcohol consumption in alcohol-preferring rats. It did so by increasing the levels of a brain protein known as GDNF, or glial cell line-derived neurotrophic factor. “By identifying the brain protein that ibogaine regulates to reduce alcohol consumption in rats, we have established a link between DGNF and reversal of addiction,” according to Dorit Ron, the principal investigator of the study.

“On the basis of word of mouth, the ibogaine scene has quadrupled in the last five years,” Ken Alper of the New York University School of Medicine told Science News. In a report published in the Journal of Ethnopharmacology, Alper reported that an estimated 850 people had taken ibogaine in 2001. By 2006, the number had risen to almost 5,000, says Alper—and almost 70 per cent of users had taken the drug for its anti-addiction properties.

Recognition of anti-craving potential for this drug has been understandably slow to reach the mainstream science world. For one thing, ibogaine remains illegal in the United States. No so in Canada, Mexico, and other countries, where ibogaine clinics have begun to appear.

Emerging insights in the brain sciences had changed the field considerably, and, unlikely as it may seem, the proponents of ibogaine managed to catch NIDA’s ear this time around. They also got a running start on some straightforward clinical research from Dr. Deborah Mash of Miami University, who gained approval for clinical trials of ibogaine for the treatment of heroin addiction. Dr. Mash now runs an ibogaine treatment clinic for heroin addicts on the island of St. Kitts.

Taking Ibogaine or any other psychedelic is a strenuous undertaking, involving altered mental states wholly unlike other drug experiences There has never been anything predictable about the results of a psychedelic trip. Since outcomes can vary so markedly, depending upon set and setting, personality, and behavioral traits, studies are difficult to design, and always have been. In the Science News article by Brian Vastag, Frank Vocci, director of anti-addiction drug development at the National Institute of Drug Abuse (NIDA), said that “The idea of trying to push this into pharmaceutical development is a tough nut."

Photo credit: http://www.chm.bris.ac.uk/motm/ibogaine/ibogainej.htm

Medical Marijuana Can Get You Fired

California Supreme Court sides with Feds.

The California Supreme Court ruled on Thursday that employers have the right to fire workers who test positive for marijuana—even if the pot is being used in line with California’s medical marijuana statutes.

In a 5-2 decision, the Court said that a Sacramento company had the right to fire an employee who tested positive for marijuana on a routine drug test, even though the employee had a letter from his physician recommending the use of marijuana for chronic pain due to a back injury suffered in the Air Force.

Justice Kathryn Werdegar, writing for the majority, made clear the legal tangle created when California voters passed an initiative in 1996 allowing the use of marijuana for medical purposes: “No state law could completely legalize marijuana for medical purposes because the drug remains illegal under federal law, even for medical users.”

Last year, a San Francisco federal court ruled that a woman with a brain tumor did not have a fundamental right of access to marijuana for medical treatment. In addition, the Drug Enforcement Administration (DEA) shut down several medical marijuana dispensing centers and made several arrests for felony distribution. Yesterday’s ruling bolsters the contention that federal law trumps state statutes.

The Pacific Legal Foundation filed a brief in support of the employer’s position in the case. “What are they supposed to do?” said Pacific Legal Foundation’s Deborah LaFetra. “Employers are held liable all the time when drunk or stoned employees cause trouble, either in the workplace or driving home.”

A spokesperson for Americans for Safe Access, a medical marijuana advocacy group based in Oakland, said they would go back to the California State legislature seeking to protect workers who use pot for medical reasons. According to the group, at least 200,000 workers in California may now be using marijuana under a doctor’s recommendation. “We remain confident that there will be a day when medical marijuana patients are not discriminated against in the workplace,” the spokesperson said.

photo credit: In These Times
http://www.inthesetimes.com

medical marijuana

FDA Puts Coke/Meth Treatment on Fast Track

Sabril may block cravings for stimulants.

The U.S. Food and Drug Administration (FDA) has given Fast Track designation to vigabatrin, an anticonvulsant marketed as Sabril, for evaluation as an anti-craving drug for cocaine and methamphetamine addiction. If approved, it would be the first medication ever approved for the treatment of addiction to stimulants.

The Fast Track designation at the FDA is intended to speed up the evaluation of drug treatments aimed at life-threatening disorders for which no current treatments exist. A 2006 study by the Substance Abuse and Mental Health Services Administration estimated that there were more than one million cocaine and methamphetamine addicts in the U.S.

First synthesized as a drug treatment for epilepsy in 1974, Sabril increases brain levels of the neurotransmitter GABA, an inhibitory compound also implicated in alcoholism. According to a press release from Ovation Pharmaceuticals, a marketer of the drug, “Sabril may block the euphoria associated with cocaine administration in humans and may suppress craving by increasing brain levels of gamma-aminobutyric acid (GABA).” Catalyst Pharmaceutical Partners has also announced plans to proceed with Sabril testing.

Ovation is collaborating with the NIDA on Phase II studies to evaluate the safety of Sabril, with Phase III trials scheduled for the end of this year. FDA has never approved the drug for use in the U.S., citing concerns over retinal damage in patients overseas.

Earlier animal testing and two limited early-stage studies on human addicts in 2003-2004 have convinced the company that Sabril diminishes cravings for stimulants. It may also blunt the euphoric effect of meth and cocaine. "This is unheard of in addiction treatment," Stephen Dewey of the Brookhaven National Laboratory, a member of an earlier vigabatrin study team, told New Scientist in 2003. "There are no medicines that are effective at blocking cocaine craving in addicts."

Writing in the November 2004 issue of Synapse, Jonathan D. Brodie and colleagues at the New York University School of Medicine reported that “A rapid elevation in nucleus accumbens dopamine characterizes the neurochemical response to cocaine, methamphetamine, and other drugs of abuse. CITE Previously, we demonstrated that this response and associated behaviors are attenuated or even blocked by Vigabatrin, an antiepileptic drug and an irreversible inhibitor of GABA-transaminase."

However, the New Scientist also reported that many doctors who work with cocaine addicts were skeptical. "Cocaine is a recreational drug. The vast majority of people who take cocaine or crack want to continue doing so," said Allan Parry, a drug counselor in Liverpool, UK. "So in that sense this work is only likely to be relevant to a tiny minority of people. People often give up cocaine because their lifestyle changes or they just grow up."

Ovation said it was “pleased that the FDA has recognized the significant need for effective treatment options to address stimulant addiction, which is a major public health problem.”

Since there are no FDA-approved medications for cocaine or methamphetamine addiction, current treatment strategy centers on cognitive and behavioral approaches.

Cocaine is Cocaine: New Sentencing Guidelines

U.S. Supreme Court relaxes jail time for crack crimes.

In a little-noted ruling last month, the U.S. Supreme Court bowed to reality and restored a measure of sanity to cocaine sentencing guidelines. The Court ruled, on a 7-2 vote in the case of Kimbrough v. U.S., that federal judges had the discretion to reduce prison terms for crack-cocaine offenses.

The move was an effort by the Supreme Court to bring crack cocaine sentences more in line with sentencing guidelines for powdered cocaine. Many drug experts expressed relief, noting that the changes were long overdue. “There’s no scientific justification to support the current laws,” said National Institute of Drug Abuse (NIDA) director Dr. Nora Volkow.

Writing for the majority, Judge Ruth Bader Ginsburg noted that the two substances in question “have the same physiological and psychotropic effects.” A number of federal judges have long advocated the change, the importance of which was demonstrated when the U.S. Sentencing Commission announced that as many as 20,000 federal inmates serving time for crack possession may be due for sentence reductions, based on the new ruling.

A 1986 law, the Anti-Drug Abuse Act, reset mandatory minimum sentences for cocaine, allowing for as much as a 100-to-1 disparity between prison time for crack and prison time for powdered cocaine. As an article in the International Herald Tribune noted, the law allowed a prison term of “five years for trafficking in 5 grams of crack, or less than the amount in two packets of sugar. It would take 100 times as much cocaine [in powder form] to get the same sentence.”

Several bills with a similar aim have been introduced in Congress, including legislation jointly sponsored by Senators Edward Kennedy and Orrin Hatch, which would revise the crack-powder sentencing ratio to 20-1.

This Alice-in-Wonderland situation was triggered by the cocaine-related death of college basketball star Len Bias in 1986. The widely publicized death set off a cocaine panic in America that quickly reached the White House and Congress. In addition, doctors and the press were busy wildly overestimating the number of handicapped “crack babies” being born. Craig Reinarman, author of the book, “Crack in America,” told the Associated Press: “You had politicians manipulating fear, and instead of being seen as a more direct mode of ingestion of a very old drug, [crack] became a demonic new substance.”

Moreover, civil rights advocates have long claimed that the sentencing structure is racist: Blacks prefer crack and Whites prefer powder, if arrest records are any indication. (Crack is produced by dissolving powdered cocaine and baking soda in water, then boiling away the water.)

According to Graham Boyd of the American Civil Liberties Union (ACLU) drug law reform project, “This may be the first sentencing decision since the mid-1980s that actually talks about justice, that seems to have some blood in it.”

“There is a sense of a turning point,” Jack B. Weinstein, a federal district court judge in New York, told Newsweek. “The cost [of the current drug war] is tremendous, to the community and to taxpayers.”

Justices Clarence Thomas and Samuel Alito dissented in the case.

Vote of No Confidence For Prometa

Addiction drug loses major funding.

It is composed of three common and inexpensive drugs used for other purposes. It has never been subjected to clinical double blind testing. It costs thousands of dollars for the full treatment package, and the company that markets it says it cures about 80 percent of the drug addicts who use it.

If that description sounds familiar—if it seems to give off a faint whiff of blue-green algae and multi-level marketing—such concerns have not stunted the promotion and acceptance of the anti-addiction drug Prometa. But MSNBC reported last week that Prometa, the drug “cocktail” designed to combat addiction to cocaine and methamphetamine, was dealt a severe blow when accountants in Pierce County, Washington froze the funding for an $800,000 pilot program, citing irregularities in testing.

The treatment involves intravenous infusions of Flumazinil, a reversal agent for benzodiazepines like Valium and Klonopin. The second drug, hydroxyzine, is an antihistamine, and the third, sold as Neurontin, as an anti-seizure medication frequently used “off prescription” as a treatment for a number of ailments, including alcoholism and hearing loss.

The treatment does not require approval by the Food and Drug Administration (FDA) because all three ingredients are already in common use in clinics and hospitals. The Prometa Regimen marketed by Hythium involves formulating the protocol and contracting with doctors to deliver the medications.

To date, there is no published clinical data to support treatment for addiction with these three drugs in proprietary combination.

Marketed heavily by anecdote and personal testimonials, the Prometa marketing campaign included ads in 2006 featuring the late comedian Chris Farley, who died of a drug overdose.

Hythiam, the company that markets Prometa, has touted the treatment with claims of success rates as high as 98 per cent, but Pierce County Councilman Shawn Bunney found the results of the county audit “alarming,” according to MSNBC. “It’s clear to me that we are much more involved in a marketing scheme…”

Hythiam Executive Vice President Richard Anderson disagreed. “The people who are using it,” he said, “the doctors, patients, administrators, and drug court judges—are seeing an impact with it, so I think the treatment will carry it at the end of the day.”

The dispute centers on the manner in which dropouts were counted in surveys done by Hythiam’s non-profit arm, the Pierce County Alliance. The Alliance had been responsible for administering the Prometa program in Pierce County drug courts. According to county auditors, dropouts and no-shows (patients who fail to show up for drug testing) were not included in the Alliance’s final report on 35 patients over a 14-month period. In Pierce and neighboring counties of Washington, drug courts record no-shows as equivalent to positive drug tests. This was not how the alliance scored it, although alliance spokespeople have insisted that county officials have misunderstood the mechanics of the study.

An investigation by the Tacoma News Tribune threw more cold water on the Prometa numbers. “According to the multiple public statements by the alliance,” wrote Sean Robinson, 86 percent of the Prometa clients ‘remained drug-free’ at the end of the 14-month program. According to county auditors, the number was 50 percent.”

Furthermore, the alliance “defined success in the Prometa program as 60 or more days of clean drug tests…. In Pierce County, drug-court clients must show 90 days of clean drug tests… In Snohomish and Thurston counties, drug-court clients must show six months.”

Investors in Hythiam, which is publicly traded, were counting on the Pierce program after similar programs in Fulton County, Georgia, and in Idaho failed to get off the ground. Things only got worse when the Tacoma News Tribune revealed that several county officials who had gotten behind the program also owned Hythiam stock.

Small rural communities that have felt the impact of meth sales and production in their communities are looking for help, and represent a significant market for an anti-addiction medication. However, in the case of Prometa, “The marketing is way ahead of the science,” claimed Lori Karan of the Drug Dependence Research Laboratory at the University of California-San Francisco.

Double-blind studies of Prometa are underway at the University of California-Los Angeles and at the University of South Carolina.

Cocaine Prices Climb, U.S. Drug Czar Declares A Win

NPR Investigation Suggests Otherwise.

It’s hard to win a war on drugs. Success stories are few, so it is not surprising that a temporary hike in recent cocaine prices in selected American cities was seized upon by U.S. Drug Czar John Walters as the lynchpin of a promotional campaign touting a victory in the war on drugs. After the U.S Coast Guard’s seized a record 160 metric tons of cocaine in early December, Walters declared: “These seizures are having a profound effect on availability of drugs in the U.S.”

But are they? In late December, National Public Radio (NPR) undertook an investigation of this claim by contacting the police departments in the 37 cities—including Los Angeles, San Francisco, Minneapolis, and Milwaukee--in which Drug Czar Walters claimed that interdictions had seriously disrupted cocaine supplies. Police officials in ten of the cities, including New York and Atlanta, confirmed that a cocaine scarcity existed. Some cities declined to respond. Five cities reported no signs of shortage, and police officials in 18 other cities gave “qualified responses,” according to NPR.

For example, officials in Boston, Chicago and Washington, D.C., acknowledged some scarcity, but said that the price and availability of rock cocaine on the street had remained essentially unchanged. Police in Detroit and Pittsburgh scoffed at the notion that cocaine was in short supply in their cities. “I spoke to my detectives out there in the streets making buys,” said Police Commander Sheryl Doubt, “and we all kind of agreed that if there’s a shortage here in Pittsburgh, we are not aware of it and don’t find that necessarily to be true.”

Police in Dallas and San Diego said they were unaware of any cocaine shortages in their cities. In San Antonio and Jacksonville, prices had gone up, but retail cocaine was readily available. In Philadelphia, Denver, and Houston, prices increased last summer, but have largely returned to normal, city officials told NPR.

Overall, said NPR, “The results suggest how difficult it is for law enforcement to create any long-term disruption in retail sales in America, which is the largest cocaine market in the world.”

Nonetheless, a stubborn Michael Braun, Chief of Operations for the Drug Enforcement Administration (DEA), said: “I don’t believe that we’ve ever seen this price/purity phenomenon over a 10-month period. This could all change next month. I hope that it doesn’t. I don’t think it will.”

But it did. In a statement not for attribution, an official at the National Drug Intelligence Center told NPR: “Cocaine availability appears to have returned to previous levels in some, but not all, drug markets, as traffickers re-establish stable sources of supply and distribution networks.” In Philadelphia, showcased as a major federal success story in choking off cocaine supplies, Police Captain Christopher Werner reported a recent bust involving 16 pounds of cocaine and more than $100,000 in cash “So,” Werner said, “is there a cocaine shortage right now? I don’t believe so.”

Even when drug wars seem to be working, and demand goes down, lowered usage of a particular drug often disguises the fact that a new drug has replaced it. There is an essential flaw in the logic behind the drug war. Demand for drugs is like a balloon--squeeze it in one place, and it bulges out somewhere else. Police officials contacted by NPR reported that wherever spot shortages of cocaine existed, “regular users turn to meth, heroin, prescription, drugs, and high-potency marijuana. In other words, enforcement had not appeared to curtail demand—one of the chief aims of the war on drugs.”

John Carnevale, a former budget director under four different drug czars, told NPR that there have been “occasional moments where we’ve seen spikes in cocaine prices… but eventually the trend continues to decline.” Such fleeting price changes, Carnevale contends, do not meaningfully affect overall demand and usage.

If it all sounds familiar, it should. By the early 1990s, after having spent more than $100 billion dollars over the preceding ten years, the Reagan-Bush drug war had almost no lasting successes to report. Interdiction at the border was a joke, cocaine and heroin were cheaper than ever, and people addicted to alcohol, cocaine, and other drugs were still committing the majority of violent crimes. Treatment for drug and alcohol addiction in prison was still an afterthought. After the “just say no” years of the Reagan administration, and the “lock ‘em up,” policy thrust of the senior Bush years, many policy reform advocates were buoyed by Bill Clinton’s election and his ardent backing of treatment on demand (which never came to fruition).

Topamax for Alcoholism: A Closer Look

Epilepsy drug gains ground, draws fire as newest anti-craving pill

A drug for seizure disorders and migraines continues to show promise as an anti-craving drug for alcoholism, the third leading cause of death in America, the Journal of the American Medical Association (JAMA) reported in its current issue.

371 male and female alcoholics between the ages of 18 and 65 took part in the study. The subjects received either topiramate or a placebo. Over 14 weeks, patients taking topiramate showed a significantly higher rate of abstinence for 28 consecutive days or more. (Rates of abstinence increased slightly in the placebo group as well. Both groups received some psychological counseling.)

Topamax is currently only approved by the Food and Drug Administration (FDA) for use against seizures and migraine. The controversial practice of “off-label” prescribing—using a drug for indications that are not formally approved by the FDA—has become so common that Johnson & Johnson (JNJ) said it had no plans to seek formal approval for the use of Topamax as a medicine for addiction.

In an editorial accompanying the study, published in the October 10 issue of JAMA, Mark Willenbring of the National Institute on Alcohol Abuse and Alcoholism (NIAAA) wrote: “We now have very high-quality evidence that shows efficacy. The medical world doesn’t wait for the indication. Topamax is a drug that many physicians have used and many patients have had an experience with because of its use in migraines.”

In addition, Topamax is already prescribed off-label in some cases for depression and Post Traumatic Stress Disorder, according to reports.

At present, there four medications legally available by prescription for alcoholism: disulfiram (Antabuse), SSRIs (off-label), naltrexone (Revia and Vivitrol), and acamprosate, the latest FDA-approved entry. Acamprosate binds to both GABA and glutamate receptors. Acamprosate, marketed in the U.S. as Campral, has been widely used in Europe on problem drinkers.

Dr. Bankole Johnson, chairman of Psychiatry and Neurobehavioral Sciences at the University of Virginia, told Bloomberg News that Topamax does everything researchers want to see in a pharmaceutical treatment for alcoholism: “First, it reduces your craving for alcohol; second, it reduces the amount of withdrawal symptoms you get when you start reducing alcohol; and third, it reduces the potential for you to relapse after you go down to a low level of drinking or zero drinking.”

According to Forbes.com, “The drug isn’t cheap—it costs about $1,000 for three months, according to Johnson. “And, patients, don’t see benefits for two to four weeks.”

Moreover, Topiramate is not without serious side effects for some users, including vision problems, difficulty remembering words, and a tingling in the arms and legs known as parasthesia.

The study was funded by Ortho-McNeil-Janssen, the subsidiary of Johnson & Johnson that produces and markets Topamax. Citing this and other alleged irregularities, Public Citizen’s Sidney Wolfe, Director of the Health Research Group, sent a stinging letter to the FDA demanding that the agency “stop the illegal and dangerous promotional campaign by Ortho-McNeil-Janssen-funded researchers for the unapproved use of Topamax (topiramate) for treating alcoholics.”

And to make things even more interesting, drug developer Mylan (MYL) received FDA approval last month for a generic form of Topamax, seeking a share of the estimated $50 million in annual sales the drug currently enjoys.

Like Campral, Topamax causes changes in the GABA and glutamate systems, which in turn affect dopamine and serotonin function. Acamprosate, like topiramate, harkens back to earlier work on GABA transmission in alcoholism. Both drugs attack the craving and relapse dilemma by stimulating GABA, the inhibitory transmitter that is the target of benzodiazepines like Valium, Xanax and Klonopin. However, Campral is not sedating. There is no buzz, no psychoactive effect, and no evidence of abuse potential whatsoever. Major side effects of acamprosate include gastrointestinal cramps and diarrhea. In addition, Campral may also “restore receptor tone” in the hyperactivated glutamate system of the alcoholic, specifically in the nucleus accumbens.

In a dozen clinical trials conducted in Europe, involving thousands of alcohol abusers, 50 per cent of acamprosate users maintained sobriety for three months without relapse, compared to 39 per cent of the placebo group. (The distressingly low numbers are testimony to the fierce mechanism of relapse.)

Topamax shows a similar mechanism of action. Earlier, researchers from the University of Texas conducted topiramate studies at the South Texas Addiction Research and Technology Center, later published in Lancet. Alcoholic patients achieved a rate of continuous abstinence six times higher than those in a placebo group did. They also reported fewer cravings, compared to a placebo group.

The downside to Topiramate may prove to be side effects. The NIAAA’s Raye Z. Litten, chief of treatment research, believes that the drug may ultimately be a strong player. “On the other hand,” he cautions, “Topiramate appears to have more severe side-effects than naltrexone and acamprosate.” Litten argues that greater efforts at testing are needed.

The National Institutes of Health (NIH) estimated that it would be sponsoring more than 30 new clinical trials of drugs for alcoholism in the next few years. The JAMA editorial, “Medications to Treat Alcohol Dependence,” concludes that the pace of development for alcoholism drugs in increasing. “A solid understanding of the neurobiology of alcohol addiction is providing the framework for multiple avenues of further medication development.”