Methamphetamine: An Excerpt

There’s more than one kind of monster.

Type and I pass the pipe.  The overhead light flickers and the wind picks up even more. It’s coming from the north because with each exhale, the smoke slips past my face, back toward the Twin Cities and my dead parents.
 
But for a brief moment, I’m not thinking about all that. I’m feeling the closest thing I can think of to God and he’s playing the samba inside of my body, his fingers gentle, as they press on the backs of my retinas, my spine, the tendons along my hip flexors. I’m thinking that I love drugs more than anything. That they are the one and only constant in my life. Yeah, they demand a lot of attention and effort, but their love is legendary, their compassion endless. I hold each hit for hours, exhale for decades. The determination that comes with the onset of a high rushes back and I’m all about conquering the world and making money and finding happiness in the form of a loving woman who knows when it’s time to brush the backs of her nails across my cheek and then I’m thinking about this being the same thing as what God is doing to me now.

I love it when my heart rattles against my uvula.

I love it when my vision is a camera shutter.

I love it when I know that someday, I will do great things.

I love it when methamphetamines make things okay.

But I don’t love it when I start to hallucinate because the line between knowing it’s only the drugs and knowing your psyche is about to snap the fuck apart like a high wire is oh so delicate....

—From Fiend, a novel by Peter Stenson

Meth Use Trending Downward, Say Feds.

Big drop registered from 2004 to 2008.

The history of illegal drug use in America is a history of peaks and valleys, with various drugs gaining ascendency and popularity for various reasons at various times--even though none of them ever go away for good.

It would be foolish to say that methamphetamine use has peaked and is on its way out. However, there is at least some evidence that in the U.S., meth may be following the same recent trend line as cocaine.

SAMHSA, the Substance Abuse and Mental Health Services Administration, regularly gathers figures related to drug use through its Drug Abuse Warning Network (DAWN) and through the National Survey on Drug Use and Health.  Between 2002 and 2006, the number of people who had used meth in the past year fluctuated from 1.6 to 1.9 million users. By 2008, however, that number had decreased to 850,000, SAMHSA has concluded. As reasons, the agency cited the 2005 law limiting sales of pseudoephedrine and ephedrine, as well as “supply and demand reduction efforts,” presumably a reference to the drug war.

As for hospital visits, “admissions for primary use of methamphetamine increased steadily from 54,000 admissions in 1994 to 154,000 admissions in 2005 and then declined to 137,000 admissions in 2007.”  Emergency department visits involving methamphetamine accounted for 8% of total drug-related visits in 2004, compared to 3% of emergency department visits for drug abuse or misuse in 2008.

As always, it is important to remember that most drug-related emergency room visits involve the use or overuse of more than one drug at a time. This changes the picture substantially, in some cases. For example, fully one-third of methamphetamine-related emergency department visits involve “methamphetamine combined with two or more other drugs,” the report discloses. A quarter of the visits also involved the use of alcohol. In 6 out of ten cases, the subjects were treated and released.

One optimistic but puzzling thought the report offers is that some improvements may be attributable to a growing awareness that “treatment providers and researchers have demonstrated that methamphetamine addiction—which once was thought untreatable—can be effectively addressed.”

I am not sure what SAMHSA means when it states that meth addiction was once considered untreatable—I am not aware of any substance addiction which cannot be “effectively addressed,” at least some of the time. And while I am always a bit wary of widespread number gathering, any indication of a decreasing interest in speed is always good news. Furthermore, if there is growing awareness that addiction to meth can be tackled successfully, just like addiction to any other drug, so much the better.

Photo Credit: SAMHSA

Methland: Book Review

Cooking crystal in the heart of the Heartland.

It’s summer, and I’ve been catching up on my reading. In an earlier post, I reviewed Joshua Lyon’s memoir of prescription drug addiction, Pill Head. This time, we travel to the opposite end of the spectrum and take a look at Methland, Nick Reding’s journalistic account of crystal meth addiction in the small farming community of Oelwein, Iowa.

This is a tale not far from my heart or home. I was born in Iowa and lived there until I was 21. A few years ago, the small Iowa town where my parents live was rocked by a series of revelations about a local lawyer’s ties to a major methedrine operation. Money had flowed through my parent’s small town in ways never seen before.

Also a few years ago, a Chippewa Indian was bound to a chair in the woods, tortured, and finally murdered in a dispute with meth dealers over some missing money. This happened about 30 miles from my home in rural Minnesota. It happened about an hour’s drive from the birthplace of Bob Dylan. It happened in a place where such things just don’t happen.

In a bleak nutshell, Reding lays out how it went down: During the lifetime of the average Baby Boomer, the amphetamine picture has evolved from the classic long-haul trucker’s Benzedrine and Dexedrine to the tweaker’s bathtub crank and crystal meth. “Not only in Oelwein, but all across Iowa, meth had become one of the leading growth sectors of the economy. No legal industry could, like meth, claim 1,000 percent increases in production and sales in the four years between 1998 and 2002, a period in which corn prices remained flat and beef prices actually fell.” In 2004, law enforcement officials busted a total of 1,370 methamphetamine labs in Iowa.

We learn about Jarvis, an Oelwein meth cook who became a local legend by staying awake on speed for 28 days, or, as Reding puts it, “an entire lunar cycle.” We hear about two-year old Buck, Iowa’s most famous meth baby, whose hair, when tested at the behest of the state Department of Human Services, recorded the highest cell follicle traces of speed ever found in an Iowa child (“At least 7,000 kids were living every day in homes that produce five pounds of toxic waste, which is often just thrown in the kitchen trash, for each pound of usable methamphetamine”). And there is the local doctor, forced to deal with meth addicts while battling his own alcohol and nicotine addictions. The doctor refers to the town’s many bars as “unsupervised outpatient stress-reduction clinics that serve cheap over-the-counter medications with lots of side effects.”

The local prosecuting attorney, we learn, has turned to Kant for solace. “So you can put a tweaker in prison,” he tells the author, “and the whole time he’s in there, he’s thinking of only one thing: how he’s going to get high the day he’s out. He’s not even thinking about it, actually. He’s like, rewired to KNOW that everything in life is about the drug. So you say, ‘What good does prison do?’”

The switch from ephedrine to pseudoephedrine as a main ingredient—an artful end run around loophole-ridden legislation—was the “blockbuster moment in the modern history of the meth epidemic,” Reding writes. “This, really, is the genius of the meth business. Cocaine and heroin are linked to illegal crops—coca and poppies respectively. Meth on the other hand is linked in a one-to-one ratio with fighting the common cold.” Moreover, half of the world’s pseudoephedrine supply is manufactured in China, far from the effective reach of U.S. law enforcement.

Not all of Iowa’s meth is homemade. California is the link between Iowa meth and the Drug War. A DEA officer tells Reding: “Our success with Medellin and Cali essentially set the Mexicans up in business, at a time when they were already cash-rich thanks to the budding meth trade in Southern California.”

The connection between Iowa meth, immigration problems, and the food industry is a bit subtler. Agribusiness consolidation in food packaging and processing—particularly meat packing--led to the demand for cheaper labor, which lead to an influx of south-of-the-border immigrants, legal and illegal, to many of Iowa’s small towns. “The real impetus to walk across the desert: Cargill-Excel in Ottumwa is always hiring,” Reding notes. Narcotics and poverty, says the author, mutually reinforce one another.

Graphics Credit: http://abouttheaddict.wordpress.com/

Meth Babies—Fact or Fiction?

Research team finds brain abnormalities.

When it came to babies born to crack-addicted mothers, the media went overboard, creating a crisis in the form of an epidemic that never quite was. By contrast, when it came to babies born to alcoholic mothers, Fetal Alcohol Syndrome went unrecognized in the science and medical community until 1968.

Now comes a study on prenatal methamphetamine exposure in The Journal of Neuroscience, headed up by Elizabeth Sowell of the University of California, Los Angeles, with support from both the National Institute on Drug Abuse (NIDA) and the National Institute of Alcoholism and Alcohol Abuse (NIAAA.) The report garnered considerable media attention. “We know that alcohol exposure is toxic to the developing fetus and can result in lifelong brain, cognitive and behavioral problems,” Sowell said in a press release. “In this study, we show that the effects of prenatal meth exposure, or the combination of meth and alcohol exposure, may actually be worse.”

It makes sense that meth might effect the health of unborn children.  There is a modest body of research to support the notion. The Sowell study points a finger at the caudate nucleus, a brain region involved with learning and memory.  The study showed that the caudate nucleus of the meth-using group was reduced in size. “Identifying vulnerable brain structures may help predict particular learning and behavioral problems in meth-exposed children,” the press release optimistically states. And the potential problem is real enough: More than 16 million Americans have used meth, according to government numbers. An estimated 19,000 of these users are pregnant women.

But is this particular study a definitive one? The icing on the cake? To begin with, the press release from The Journal of Neuroscience admits to a major problem right up front: “About half of women who say they used meth during pregnancy also used alcohol, so isolating the effects of meth on the developing brain is difficult.”  Even in cases of meth exposure only, there are a host of negative behavioral factors that often accompany meth addiction (bad nutrition, minimal health care, poor health) that can significantly effect fetal development.

The study team compared the MRI brain scans of 61 children: “21 with prenatal MA (methamphetamine) exposure, 18 with concomitant prenatal alcohol exposure (the MAA group), 13 with heavy prenatal alcohol but not MA exposure (ALC group), and 27 unexposed controls. While finding “striatal volume reductions,” as well as increases in the size of certain limbic structures in both groups with meth and/or alcohol exposure, the researchers conclude that striatal and limbic structures “may be more vulnerable to prenatal MA exposure than alcohol exposure.” However, that conclusion was apparently reached despite the fact that only 3 of the 61 children under study were born to mothers who did meth, and meth only, during pregnancy.

Furthermore, there is significant controversy over brain scan studies that measure gross anatomical changes in the size of specific brain regions, rather than brain region activity based on blood flow.

Is there other evidence for the danger of meth use during pregnancy? There is, but as is frequently the case, some of the best evidence comes from animal studies. A 2008 guinea pig study by Sanika Chirwa showed neural damage to the hippocampus, another region involved in memory, in newborn animals with prenatal meth exposure. Furthermore, the newborn animals showed an impaired ability to distinguish novel objects from familiar ones.

In 2006, a study at Brown Medical School, published in Pediatrics , found that newborns exposed to meth during pregnancy were born “small for gestational age,” meaning they were born full-term, but smaller than babies not exposed to meth in utero.  According to study author Barry Lester, “Children who are born underweight tend to have behavior problems, such as hyperactivity or short attention span, as well as learning difficulties.”

However, Lester added an important caveat in a Brown University press release : “I hope that the ‘crack baby’ hysteria does not get repeated. While these children may have some serious health and developmental challenges, there is no automatic need to label them as damaged and remove them from their biological mothers.”

Similar caution was urged by the authors of a 2009 report in the Journal of Developmental and Behavioral Pediatrics: “Efforts to understand specific effects of prenatal methamphetamine exposure on cognitive processing are hampered by high rates of concomitant alcohol use during pregnancy.”

In 2005, an open letter from the Center for Substance Abuse Research at the University of Maryland warned about the dangers of hyperbole, calling upon the media and public officials to “stop perpetuating ‘meth baby’ myths.” The Center argued that “The terms ‘ice babies’ and ‘meth babies’ lack medical and scientific validity and should not be used,” and requested that “policies addressing prenatal exposure to methamphetamines and media coverage of this issue be based on science, not presumption or prejudice.”

Sowell, E., Leow, A., Bookheimer, S., Smith, L., O'Connor, M., Kan, E., Rosso, C., Houston, S., Dinov, I., & Thompson, P. (2010). Differentiating Prenatal Exposure to Methamphetamine and Alcohol versus Alcohol and Not Methamphetamine using Tensor-Based Brain Morphometry and Discriminant Analysis Journal of Neuroscience, 30 (11), 3876-3885 DOI: 10.1523/JNEUROSCI.4967-09.2010

Smith, L., LaGasse, L., Derauf, C., Grant, P., Shah, R., Arria, A., Huestis, M., Haning, W., Strauss, A., Grotta, S., Liu, J., & Lester, B. (2006). The Infant Development, Environment, and Lifestyle Study: Effects of Prenatal Methamphetamine Exposure, Polydrug Exposure, and Poverty on Intrauterine Growth PEDIATRICS, 118 (3), 1149-1156 DOI: 10.1542/peds.2005-2564

Photo credit: http://www.psychiatry.emory.edu

Of Mice and Methamphetamine

Diabetes drug being tested for addiction.

It’s a mouthful: peroxisome proliferator activated receptor gamma (PPAR-gamma). 

Peroxisomes are specialized subunits inside cells that help metabolize various substances, including fatty acids and certain toxins. A blockbuster member of this drug family—Avandia—is a much disputed but immensely lucrative diabetes medicine that may cause heart failure.

(Partial Agonist Ppar Gamma Cocrystal)--------->

PPAR gamma agonists belong to a class of drugs known as thiazolidinediones. Clinical research has pointed toward additional therapeutic applications for thiazolidinediones in the areas of inflammation and cancer. The only approved use for thiazolidinediones is in the treatment of diabetes, but the drug class has also been studied for treatment of polycystic ovary syndrome, psoriasis, autism—and now drug addictions. A PPAR compound will soon undergo testing under the auspices of the Omeros Corporation, with funding from the National Institute on Drug Abuse (NIDA).

Omeros says it has developed a novel drug “for the prevention and treatment of addiction to substances of abuse, such as opioids nicotine and alcohol, as well as other compulsive behaviors, including eating disorders.” Phase 2 clinical studies on opiate addiction by Dr. Sandra D. Comer and associates at the New York State Psychiatric Institute will begin soon, according to an Omeros press release.

Such claims add up to a tall order for any anti-craving drug. In fact, no drug currently exists for the treatment of so wide a spectrum of addictive disorders. Nonetheless, Omeros claims to have demonstrated a previously unknown link between a variant of this family of diabetes medications and addiction.

The heart problems linked to the PPAR marketed as Avandia may be a special case. According to an article by Gardiner Harris in the New York Times, based on government reports obtained by the newspaper: “If every diabetic now taking Avandia were instead given a similar pill named Actos, about 500 heart attacks and 300 cases of heart failure would be averted every month because Avandia can hurt the heart. Avandia, intended to treat Type 2 diabetes, is known as rosiglitazone and was linked to 304 deaths during the third quarter of 2009.” Actos, another thiazolidinedione, has not been linked to any heart trouble.

 GlaxoSmithKline is disputing the findings. A number of other pharmaceutical houses—AstraZeneca, and Eli Lilly among them—discontinued their first generation PPAR drugs. The derivative marketed as Avandia is not the compound under study by Omeros.

There is little clinical evidence to bolster the PPAR theory. A recent Spanish study suggested the possibility that PPAR gene variants may be associated with higher alcohol consumption in a small sampling of Mediterranean drinkers.

The most comprehensive study may be a 2007 paper in Neuropsychopharmacology by Takehiko and coworkers, demonstrating that PPARs can have an effect on behavioral sensitization to methamphetamine in mice.

Behavioral sensitization is the name for the progressive increase in meth-driven locomotor activity over time. The researchers found that a PPAR variant “plays an inhibitory role in the expression” of sensitization to methamphetamine. The action takes place in the brain’s nucleus accumbens, where repeated hits of meth cause an increase in PPAR expression, according to the researchers: “These results indicate that [an isotope of PPAR] in the reward system is involved in behavioral sensitization to METH.”

What is the mechanism of action? The researchers speculate that upregulation and activation of PPAR in the meth-crazy mice may be due in part to an inflammatory response. PPAR, in theory, exerts anti-inflammatory activity in brain cells.  And psychostimulants, according to the researchers, “upregulate the expression of target genes via activation of inflammatory-responsive transcriptional factors.”

Maeda, T., Kiguchi, N., Fukazawa, Y., Yamamoto, A., Ozaki, M., & Kishioka, S. (2006). Peroxisome Proliferator-Activated Receptor Gamma Activation Relieves Expression of Behavioral Sensitization to Methamphetamine in Mice Neuropsychopharmacology, 32 (5), 1133-1140 DOI: 10.1038/sj.npp.1301213

Graphics Credit: http://www.prostaglandinresearch.com

Addiction Assumptions: The Meth Epidemic

Who is really at risk?

A simple question: Has meth use in the United States truly reached “epidemic” levels, as is commonly stated by health authorities and drug experts?

The answer depends on how you slice the data, according to sociologist Herbert Covey. For women, unemployed men, and residents of the Western United States, the answer is yes. For African-Americans and citizens of the Northeast, not so much.

In “Prevalence of Use and Manufacture of Methamphetamine in the United States,” published in the Praeger International Collection on Addictions, Dr. Covey first notes that the spread of methamphetamine use is by no means unique to the United States. In Thailand, Covey writes, more than 70 percent of the addict population is composed of meth users.

In the U.S., meth lab busts increased 4,000 percent from 1995 to 2001, according to the Office of National Drug Control Policy. Treatment numbers also soared, but it is not clear whether this trend represents more meth users, or more court-mandated treatment for offenders.

The short answer to the question of who is at primary risk is: women. According to Covey, women of childbearing age represent a severely problematic risk group. Women report using meth at an earlier age, have significantly longer first treatment experiences, and have greater difficulty than men with related issues of employment, child-raising, and job opportunities. (See my post on “Rehab and the Working Mother.”)

Perhaps the most unwelcome finding of all is that “The majority of women [in a major study of gender differences] had children under 18, but most did not live with their children within the last 30 days.”

However, there is a tendency in the media to leap ahead of the data with stories of this sort. Covey and other researchers question the validity of media references to “meth babies” and “ice babies,” recalling the overblown coverage of the “crack baby” epidemic of the 1980s—an epidemic for which, more than two decades later, there is almost no solid evidence. As Covey cautions, “that meth use by pregnant women results in severe health consequences for infants has not been established by medical research.”

As Covey sums it up: “Meth accounts for a small percentage of the total number of people affected by drug and alcohol problems. However, almost all of the data... reveal that meth use, manufacturing and distribution are increasing throughout much of the nation.” In the future, he writes, “The other question is whether meth use will grow in prevalence in minority populations. To date Latino, Hispanic, and African American populations have not embraced meth to the extent that Anglos have. If this changes, the negative effects could be substantial.”

Covey concludes: “Whether the upward spiral of meth use and manufacture continues remains to be seen.”

Photo Credit: The Curvature

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Guest Post: Things Go Better with Meth

The Pepsi Challenge with controlled substances.

[Today’s post comes to us from Neurological Correlates, a blog devoted to the neuroscience of dysfunctional behavior. It was written by Swivelchair, who refers to himself as “an anonymous biopharma worker." It’s an excellent blog, one of the few that focuses on the biological basis of addiction.]
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Things go better with meth, as compared to cocaine, if you’re dopamine transporter challenged, anyway.

By Swivelchair

Methamphetamine is taken up more quickly, and lasts longer than cocaine. (Fowler et al, Abstract below).

And here’s something from Microgram Bulletin, October 2008, Published by the Drug Enforcement Administration Office of Forensic Sciences Washington, D.C. 20537: The DEA South Central Laboratory (Dallas, Texas) recently received a submission of approximately 4972 fake “kidney beans” (total net mass 3,210 grams), all containing a fine tan powder, suspected heroin. The “beans” were actually small plastic packets that had been painted to resemble kidney beans... Analysis of the powder... confirmed 90.3% heroin hydrochloride.

The perhaps undeniable point: probably the self-selecting population of people who are first drawn to drugs, and then become irretrievably addicted, are those who lack sufficient dopamine transport to feel fulfilled (or other insufficiency, depending on the choice of drug). They are, in essence, self-medicating, rather than using drugs for recreational use. I mean, you don’t load up kidney beans for recreational drug users.

I’m reminded of a friends’ younger brother, from a locally well-known family, whose arrest was reported as bringing in “the largest amount” of cocaine in those parts. His remark: He was a wholesaler, and the newspaper quoted street (”retail”) values, so the report inflated his inventory value. This was purely about money for him — he made far more money selling coke than any job he was qualified to do (which was, well, probably none, unless being a bon vivant and sparkling raconteur with insufficient money to fund a high rent party lifestyle qualifies as a profession, which it may). If the US were to decriminalize drug use, and fund a program to make an agonist which was not addictive (a la the whole methadone thing), probably we could solve much of the crime problem in the Western Hemisphere.
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“Fast uptake and long-lasting binding of methamphetamine in the human brain: comparison with cocaine.” Fowler JS, Volkow ND, Logan J, et. al. Medical Department, Brookhaven National Laboratory, Upton, NY 11973

Abstract from Neuroimage. 2008 Dec; 43(4):756-63.

“Methamphetamine is one of the most addictive and neurotoxic drugs of abuse. It produces large elevations in extracellular dopamine in the striatum through vesicular release and inhibition of the dopamine transporter. In the U.S. abuse prevalence varies by ethnicity with very low abuse among African Americans relative to Caucasians, differentiating it from cocaine where abuse rates are similar for the two groups. Here we report the first comparison of methamphetamine and cocaine pharmacokinetics in brain between Caucasians and African Americans along with the measurement of dopamine transporter availability in striatum.

Methamphetamine’s uptake in brain was fast (peak uptake at 9 min) with accumulation in cortical and subcortical brain regions and in white matter. Its clearance from brain was slow (except for white matter which did not clear over the 90 min) and there was no difference in pharmacokinetics between Caucasians and African Americans. In contrast cocaine’s brain uptake and clearance were both fast, distribution was predominantly in striatum and uptake was higher in African Americans. “Among individuals, those with the highest striatal (but not cerebellar) methamphetamine accumulation also had the highest dopamine transporter availability suggesting a relationship between METH exposure and DAT availability. Methamphetamine’s fast brain uptake is consistent with its highly reinforcing effects, its slow clearance with its long-lasting behavioral effects and its widespread distribution with its neurotoxic effects that affect not only striatal but also cortical and white matter regions. The absence of significant differences between Caucasians and African Americans suggests that variables other than methamphetamine pharmacokinetics and bioavailability account for the lower abuse prevalence in African Americans.”

Related Links

PET studies of d-methamphetamine pharmacokinetics in primates: comparison with l-methamphetamine and ( –)-cocaine. [J Nucl Med. 2007] PMID:17873134

Long-term methamphetamine administration in the vervet monkey models aspects of a human exposure: brain neurotoxicity and behavioral profiles. [Neuropsychopharmacology. 2008] PMID:17625500

Graphics Credit: methamphetaminetx.com

addiction drugs dopamine

The Pharmacokinetics of Speed

Meth lingers longer than coke, targets different brain areas.

Scientists at the Brookhaven National Laboratory, already famous for their work on positron emission tomography (PET) scans, have traced the pathways by which methamphetamine lingers in the brain longer than cocaine. The Brookhaven Lab, managed by the U.S. Department of Energy (DOE) tested non-drug abusing volunteers. The results will be published in the November 1 issue of Neuroimage.

The researchers injected the 19 volunteers with radioactively tagged doses of the drugs. Scanning cameras then recorded the concentration and distribution of the tagged molecules. Both cocaine and methamphetamine enter the brain quickly—part of the reason why the two drugs are so reinforcing. However, cocaine clears the brain just as quickly, while meth does not. Moreover, the study demonstrated that methamphetamine is much more widely distributed throughout the brain than cocaine, which tends to exclusively target the dopamine-rich limbic reward pathways. “This slow clearance of methamphetamine from such widespread brain regions may help explain why the drug has such long-lasting behavioral and neurotoxic effects,” said Joanna Fowler, lead author of the study.

The researchers also looked at a more controversial hypothesis—widespread reports that methamphetamine abuse among African Americans is markedly lower than it is among Caucasians. These reports lead Fowler and her colleagues to question “whether biological or pharmacokinetic differences might explain this difference.”

The answer? Evidently not. According to a Brookhaven press release, “Surprisingly, the researchers found significant differences in cocaine pharmacokinetics between African Americans and Caucasians, with the African Americans exhibiting higher uptake of cocaine, a later rise to peak levels, and slower clearance.” When it came to speed, however, the scientists failed to detect any racial differences in uptake.

Fowler’s conclusion: “Variables other than pharmacokinetics and bioavailability account for the lower prevalence of methamphetamine abuse in African Americans.”

She added that “the differences observed for cocaine pharmacokinetics are surprising considering there are no differences in cocaine abuse prevalence between these two ethnic groups.”

This may come as a surprise to people who have been taught by news coverage and crime dramas to think of the crack problem as a “black problem.” But it may also indicate an inherent physiological preference for cocaine among African Americans, regardless of stated levels of abuse prevalence. As usual, more studies are needed.

Image Credit: Brookhaven National Laboratory News

dopamine

No Pill for Stimulant Addiction

Meth and cocaine continue to elude researchers.

Despite promising trials of several compounds, methamphetamine addiction remains largely impervious to anti-craving pills and other forms of drug treatment. According to a paper in the June issue of Addiction Science and Clinical Practice, "currently, no medications are approved by the FDA for the treatment of stimulant dependence. However, recent advances in understanding... have allowed researchers to identify several promising candidates."

The paper's author, Dr. Kyle Kampman of the University of Pennsylvania School of Medicine and Treatment Research Center, notes that "the demand for treatment for cocaine dependence remained roughly level from 1992 to 2005, while the demand for treatment for amphetamine dependence increased about eight-fold." (See chart above).

As I wrote earlier ("FDA Puts Coke/Meth Treatment on Fast Track"), the U.S. Food and Drug Administration (FDA) in January gave Fast Track designation to vigabatrin, sold as Sabril by Ovation Pharmaceuticals. 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.

Vigabatrin, an anti-epilepsy drug called Gamma-vinyl-GABA, or GVG for short, showed early promise for use with cocaine addicts in a 60-day study and appears to increase GABA transmission. GABA has an inhibitory effect on dopamine and serotonin release.

Another entry in the vigabatrin sweepstakes, Catalyst Pharmaceuticals, is also testing its version of the drug, dubbed CPP-109, for the treatment of methamphetamine addiction in Phase II double-blind, placebo-controlled studies. Patrick J. McEnany, chief executive officer of Catalyst, commented, "We are excited to follow up on our cocaine trial with the initiation of our second, large-scale U.S. Phase II trial with CPP-109, this time as a potential treatment for methamphetamine addiction. As with cocaine, we believe that CPP-109 may offer the potential to provide patients suffering from methamphetamine addiction, as well as the physicians and clinicians that treat them, with a safe and effective pharmacotherapy option."

What, in essence, are such pills designed to accomplish? The primary avenue of research has centered upon medications that decrease the addict's experience of withdrawal and craving. According to Kampan, "several studies have demonstrated that patients who experience severe cocaine withdrawal symptoms... are twice as likely to drop out of treatment and less likely to attain abstinence in outpatient programs."

However, questions remain about the safety of vigabatrin. Although available abroad, it is not approved for use in the U.S., due to an association with serious visual effects after long-term use. The use of vigabatrin for stimulant addiction, if approved, might require associated eye examinations.

Buproprion, a drug that has shown some promise in the treatment of cocaine addiction, is also a candidate for meth addiction. The drug inhibits the reuptake of dopamine, thus allowing more dopamine to circulate in the brain. In addition, there are plans to test other drugs being investigated for cocaine craving, such as topiramate and modafinil.

According to the 2005 SAMHSA Survey on Drug Use and Health, an estimated 10.4 million people age 12 or older (4.3 percent of the population) have tried methamphetamine at some time in their lives. Approximately 1.3 million reported past-year methamphetamine use, and 512,000 reported current (past-month) use. Approximately 535,000 patients sought treatment for methamphetamine and other stimulant abuse in 2006.

Next post: Drugs for cocaine craving

Photo Credit: National Drug Intelligence Center

dopamine

Meth to the West, Cocaine to the East, Pot in the Middle

The geography of drug use.

To paraphrase an old tune by Gerry Rafferty, we got meth to the left of us, cocaine to the right, and here we are, stuck in the middle with pot.

The National Drug Threat Survey of 2007, a product of the National Drug Intelligence Center (NDIC) at the Department of Justice, illustrates the stark nature of regional variation when it comes to illegal drugs of choice in the United States. The map at the right represents the responses of state and local law enforcement agencies to the question: "What drug poses the greatest threat to your area?" Blue indicates cocaine, red indicates methamphetamine, and green stands for marijuana. (Click map for larger image.)

According to the Oregonian in Portland, reporting on similar numbers from the U.S. Substance Abuse and Mental Health Services Administration: "The politics of methamphetamine have been shaped by geography. Lawmakers from the East, Midwest and South focused on cocaine--the most heavily abused drug by far in their home states. By contrast, more than 90 percent of people treated for meth abuse live west of the Mississippi River."

The NDIC's stated mission is "to provide strategic drug-related intelligence, document and computer exploitation support, and training assistance to the drug control, public health, law enforcement, and intelligence communities of the United States...." NDIC obtains its data through direct surveys of federal, state and local law enforcement and intelligence agencies, as well as information from court documents, news sources, and public health agencies.

The NDIC has produced a National Drug Threat Survey annually since 2000, and began deriving state-level estimates in 2003. Federal, state and local government agencies use the statistical estimates as guidelines for promulgating drug legislation and enforcement strategies.

Graphics Credit: National Drug Intelligence Center

Amphetamine Blues

How meth addiction happens.

If alcohol’s impact on brain cells is wide-ranging and diffuse, and marijuana’s impact is selective and subtle, the impact of cocaine and amphetamine is much more straightforward. “There is certainly lots of evidence for common neurological mechanisms of reward across a wide variety of drugs,” said Dr. Robert Post, chief of the biological psychiatry branch at NIMH.

Animals will readily administer cocaine and amphetamine, Dr. Post once explained to me, but when researchers surgically block out areas of the brain that are dense with dopamine receptors, the picture changes dramatically. “The evidence definitely incriminates dopamine in particular,” said Dr. Post. “In animal models, if you make selective lesions in the dopamine-rich areas of the brain, particularly the nucleus accumbens in the limbic system, the animals won’t self-administer either amphetamine or cocaine.”

When you knock out large slices of the nucleus accumbens, animals no longer want the drugs. So, one cure for addiction has been discovered already—but surgically removing chunks of the midbrain won’t do, of course.

At the heart of the meth high is a chemical paradox. The entire range of stimulative effects hits the limbic system within seconds of being inhaled or inject, and the focused nature of the impact yields an astonishingly pleasurable high.

But the long-term result is exactly the opposite. The body’s natural stock of these neurotransmitters starts to fall as the brain, striving to compensate for the artificial flooding of the reward center, orders a general cutback in production. At the same time, the receptors for these neurotransmitters become excessively sensitive due to the frequent, often unremitting nature of the stimulation.

The release of dopamine and serotonin in the limbic structure called the nucleus accumbens lies at the root of active drug addiction. It is the chemical essence of what it means to be addicted. The pattern of neural firing that results from this surge of neurotransmitters is the “high.” Dopamine is more than a primary pleasure chemical—a “happy hormone,” as it has been called. Dopamine is also the key molecule involved in the memory of pleasurable acts. Dopamine is part of the reason why we remember how much we liked getting high yesterday.

One reason why amphetamine addicts will continue to use, even in the face of rapidly diminishing returns, is simply to avoid the crushing onset of withdrawal. Even though the drug may no longer be working as well as it once did, the alternative--the psychological and physical cost of withdrawal--is even worse. When addicts talk about “chasing a high,” the metaphor can be extended to the losing battle of neurotransmitter levels. In the jargon used by Alcoholics Anonymous, addicts generally have to get worse before they can get better.

Speed, then, is diabolically well suited to the task of artificially stimulating the limbic reward pathway. Molecules of amphetamine displace dopamine and norepinephrine in the storage vesicles, squeezing those two neurotransmitters into the synaptic gap, and keeping them there, where they repeatedly stimulate their receptors. By mechanisms less well identified, cocaine accomplishes the same feat. Speed also interferes with the return of dopamine, norepinephrine, and serotonin molecules to their storage sacs, a procedure known as reuptake blocking—the same mechanism by which the so-called selective serotonin reuptake inhibitors (SSRI) antidepressants increase the availability of serotonin in the brain.

Adapted from The Chemical Carousel: What Science Tells Us About Beating Addiction © Dirk Hanson 2008, 2009.

addiction drugs

Fewer People Testing Positive For Meth and Cocaine

Quest Diagnostics releases 2007 figures.

Quest Diagnostics, the nation’s leading provider of employee drug testing services, reported a 22 percent drop in the number of U.S. workers and job applicants testing positive for methamphetamine last year. The percentage of positive tests for cocaine fell 19 percent in the same period—the largest single-year decline since 1997, the company reported.

Overall, drug test positives were at an all-time low (see chart). The company said 3.8 percent of employees had tested positive for drug use in 2007, compared to a high of 13.6 in 1988.

Quest Diagnostics based its conclusions on a summary of results from more than 8 million workplace drug tests the company conducted in 2007. The data include pre-employment, random, and for-cause testing. The primary test population included federally mandated testing of “safety-sensitive” workers such as pilots, truck drivers, and employees at nuclear power plants
It is not immediately clear what conclusions can be drawn from the Quest Drug Testing Index. Do the results indicate a falloff of stimulant use, or are they a reflection of scarcities of supply?

The DEA was quick to jump in and claim the latter: “The fact that America’s workers are using cocaine and methamphetamine at some of the lowest levels in years is further evidence of the tremendous success that law enforcement is having at impacting the nation’s illicit drug supply,” Drug Enforcement Administration (DEA) Acting Administrator Michele Leonhard said in a press release.

In the same press release, Dr. Barry Sample of Quest Diagnostics, citing figures that show a 5 percent increase in the use of all forms of amphetamines last year, said: “Although some may conclude that there is a reduced availability for methamphetamine, the fact that our data show an increase in amphetamines suggests that some workers might be replacing one stimulant drug for another in the larger drug class of amphetamines.”

It is also unclear whether or not the lower numbers reflect greater employee awareness of drug testing, and greater knowledge of methods for finessing the testing system, such as a crash course of abstinence when testing is considered likely.

Moreover, drug testing remains a controversial practice. Critics maintain that the costs of drug testing far exceed the benefits of identifying a very small percentage of workers with testing procedures that are not always and inevitably reliable.

In a review of a report on drug testing by the National Academy of Sciences in 1999, the American Civil Liberties Union (ACLU) concluded: “There is as yet no conclusive evidence from properly controlled studies that employment drug testing programs widely discourage drug use or encourage rehabilitation.” According to the ACLU, the federal government spends more than $77,000 dollars for each positive drug test, when overall costs of the federal government’s drug testing program are taken into consideration.

Graphics Credit: Market Wire

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.