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

Feds Fund Study of Marijuana Withdrawal

Probing the biology of cannabis addiction.

Addiction expert Barbara Mason of the Scripps Research Institute of La Jolla, California, will oversee a four-year study of the neurobiology of marijuana dependence under a grant from the National Institute of Drug Abuse (NIDA).

The comprehensive project will involve both animal and human research, and will make use of state-of-the-art functional brain imaging. The federal grant will also be used as seed money for the new Translational Center on the Clinical Neurobiology of Cannabis Addiction at the Scripps Institute.

Mason, director of the Laboratory of Clinical Psychopharmacology at Scripps, told reporters in San Diego that the research, which will also be conducted at several universities, is important work: “People are deciding every day whether to use or not to use marijuana, for medical purposes or otherwise, and there is little scientific information to advise this decision.” Mason has previously done work on medical therapies for alcoholism, and on the connections between alcoholism and depression.

An article by Terri Somers in the San Diego Union-Tribune quoted Dr. Mark Gold, an addiction expert from the University of Florida: “While treatments have been developed for addictions from alcohol to nicotine and narcotics, none exists for the cannabis dependent. This research will help the field define what cannabis is and is not, and how to treat it.”

Among the withdrawal symptoms common to heavy pot smokers, according to Mason, are anxiety, anger, sleep disturbances, and bad dreams. In earlier research, Mason discovered that those seeking treatment for cannabis addiction tended to cluster in two age groups—college age and mid-50s.

The research coincides with a growing belief in the psychiatric community that cannabis dependence is real and verifiable, despite years of assertions to the contrary.

There is at present a small and controversial body of clinical research, which strongly suggests the existence of a marijuana discontinuation syndrome. Dr. Gold and others believe that roughly one out of every ten pot smokers is at risk for marijuana dependence and withdrawal.

Photo credit: Kevin Fung, Scripps Research Institute

See also:
Marijuana Withdrawal

Drug That Blocks Stress Receptor May Curb Alcohol Craving

Anxiety, drugs, and the brain’s “fear center.”

A brain receptor for a neurotransmitter involved in stress and anxiety has become a primary target in the scientific war on alcoholism—the only kind of drug war that really matters.

Researchers at the National Institute of Alcohol Abuse and Alcoholism (NIAAA), working with colleagues at Lilly Research Laboratories and University College in London, announced that a drug that blocks the so-called NK1 receptor (NK1R) reduced alcohol cravings in a study of 25 detoxified alcoholic inpatients. The drug “suppressed spontaneous alcohol cravings, improved overall well-being, blunted cravings induced by a challenge procedure, and attenuated concomitant cortisol responses.”

The study, published in the current issue of Science magazine, (look here for abstract) demonstrates that investigators continue to work toward more effective anti-craving drugs from a variety of angles. The NIAAA researchers are making effective use of recent findings about the role played by corticotropin-releasing hormone (CRH) in the addictive process. CRH is crucial to the neural signaling pathway in areas of the brain involved in both drug reward and stress.

Another neurotransmitter of this type is substance P, together with its preferred receptor, NK1R. As it happens, NK1R sites are densely concentrated in limbic structures of the mid-brain, such as the amygdala, or so-called “fear center.” The experimental drug, known as LY686017, blocks NK1R receptors, shutting off substance P, which in turn diminishes anxiety-related drug cravings.

Other researchers had previously demonstrated that deletion of NK1R sites eliminated opiate use in animal models. It has also been known for some time that alcohol and the opiates share certain common chemical pathways in the brain. And in humans, at least one earlier study showed decreased stress and anxiety reactions in human subjects taking a drug that blocked the Neurokinin 1 receptors.

The authors of the study suggest that “blockade of NK1Rs might modulate stress- and reward-related processes of importance for excessive alcohol use and relapse.”

According to NIAAA director Dr. Ting-Kai Li, “These findings advance our understanding of the link between stress and alcohol dependence and raise the prospect of a new class of medications for treating alcoholism.”

The early finding will require more research. “To our knowledge,” the authors conclude, “no data are presently available to address this hypothesis.”

graphic credit: http://www.ibiblio.org/rcip/ptsdmemory.html

Drug Addiction and Dissociation

Where does the “self” go during active addiction?

Where does the everyday self go during active cycles of addiction? Addiction sometimes seems to resemble a waking trance, or autohypnosis. Psychologically, it is akin to a state of dissociation. The sense of self becomes impaired through the processes of intoxication, denial, neuroadaption, withdrawal, and craving. This impaired sense of self causes behavior that is baldly contradictory to the addict's core beliefs and values. Honest men and women will lie and steal in order to get drugs.

Webster’s Unabridged Dictionary defines dissociation, rather vaguely, as “the splitting off of certain mental processes from the main body of consciousness, with varying degrees of autonomy resulting.” How autonomous were you, consciousness-wise, the last time you got drunk and parked your car somewhere you couldn’t remember?

Dissociation may be part of the way consciousness itself adapts to chronic drug use. Richard S. Sandor, a thoughtful Los Angeles physician, helped to clarify many of these issues in an excellent essay some years ago in Parabola Magazine.

Sandor compares the addictive state to a form of hypnosis accompanied by posthypnotic amnesia. This automatism, this subsequent amnesia about the drugged “I” on the part of the sober “I,” is highly reminiscent of the consequences produced by state-dependent memory:

"A hypnotized subject is instructed to imagine that helium-filled balloons are tied to his wrist; slowly the wrist lifts off the arm of the chair. The subject smiles and says, ‘It’s doing it by itself!’ The ‘I’ that lifts the arm is unrecognized (not remembered) by the ‘I’ that imagines the balloons.... One part denies knowledge of what another part does. A cocaine addict, abstinent for a year, sees a small pile of spilled baking soda on a bathroom counter and experiences an overwhelming desire to use the drug again. Who wishes to get high? Who does not?"

“Interestingly,” Sandor says, “this type of amnesia is very similar to that seen in the multiple personality disorder (see Jekyll and Hyde), in which one entire ‘personality’ seems to be unaware of the existence of another. Even more interesting is the fact that confabulation, rationalization, and outright denial are also prominent features of the addictive disorders.” Dissociation, then, can occur without the intervention of anything as dramatic as hypnosis. The common quality is automaticity, the experience of “it doing it by itself.”

Sandor points to the inability of prevailing behavioral models to produce a comprehensive framework for effective addiction treatment. “None of the current treatment methods based upon the positivist scientific paradigm—be it psychodynamics (Freud, et al.) or behavioral (Pavlov, Watson, Skinner)—has demonstrated any particular superiority in the treatment of the ‘addictive disorders,’” he writes. “Many psychoanalysts readily admit the uselessness of that method for treating addicted individuals (the patient is regarded as being ‘unanalyzable’).”

In addition, says Sandor, “It appears that the most successful means of overcoming serious physical addiction is abstinence—very often supported by participation in one of the twelve-step groups based on the Alcoholics Anonymous model.... The basis of recovery from addiction in these nonprofessional programs is unashamedly spiritual.”

All addictions, Sandor argues, more closely resemble “the whole host of automatisms that we accept as an entirely normal aspect of human behavior than to some monstrous and inexplicable aberration.” Bicycle riding is a good example of an automatism, because once learned, “…it no longer requires the subjective effort of attention; more importantly, once learned, it cannot be forgotten. It is as though the organism says to itself, ‘Riding this thing could be dangerous! It’s much too important to trust that Sandor will pay close attention to it.’”

So what does the mind do? It creates a new state called bicycle riding:

"Number one priority in this state (after breathing and a few other things, of course) will be maintaining balance. In much the same way, the organism recognizes that mind- and mood-altering chemicals disturb the equilibrium of functions and are therefore potentially dangerous. In response, it may form a new state in which the ability to function is restored, but in which a new set of priorities exerts an automatic influence. Just as one’s only hope of not riding the bicycle again (if for some reason that is important) is to never again get on one, once a particular addictive state has developed, there is no longer any such things as “one” (drink, hit, fix, roll, etc.). Addicts begin again when they forget this fact (if indeed they have ever learned it) and/or when they become unable to accept the suffering that life brings and choose to escape it without delay. Addictions can be transcended--not eliminated."


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

Paul Wellstone’s legacy

House passes Mental Health and Addiction Equity Act.

I live in Minnesota, so it is with great pride that I report that the U.S. House of Representatives recently passed mental health and addiction legislation named after the late U.S. Sen. Paul Wellstone of Minnesota, involving issues that were very close to his heart.

Wellstone, who died in a plane crash in northern Minnesota in 2002, was a two-term Democratic Senator who championed the cause of full medical insurance for the coverage of addiction treatment and mental illness. The Paul Wellstone Mental Health and Addiction Equity Act of 2007, sponsored by Rep. Patrick Kennedy of Rhode Island, passed the U.S. House on a vote of 268-148. The legislation will now be the subject of negotiations with the U.S. Senate, which earlier passed a similar but less stringent bill, sponsored by Rep. Patrick Kennedy’s father, Sen. Ted Kennedy.

Rep. Jim Ramstad of Minnesota, one of the bill’s key backers, and a recovering alcoholic, told Kevin Diaz of the Minneapolis Star Tribune: “This is not just another policy issue. It’s a matter of life and death for millions of Americans.”

The bill would require insurers to cover mental illness and addiction using the same guidelines as any other physical disease or ailment. Health insurance industry spokespeople said the bill goes too far, and would drive up health insurance premiums by mandating additional expensive treatments. The Senate version does not mandate mental health coverage, and offers exemptions for smaller group health plans.

But advocates of the Wellstone Act say that the provisions in the bill are long overdue. “We’re no longer going to allow people to languish in the shadows,” said Rep. Kennedy.

The House and Senate will also have to grapple with how the new bill will effect existing state legislation. According to Victoria Colliver in the San Francisco Chronicle, more than 25 states already have laws on the books mandating mental health coverage. Said California State Assemblyman Jim Beall Jr., who supports the Wellstone Bill: “If you don’t cover moderate mental problems or substance abuse, which often go together… you would not treat the person until their problems become acute—that’s not good health care.”

Drug Use State-By-State

Vermont leads nation in marijuana use

A new report released by the Substance Abuse and Mental Health Services Administration (SAMHSA) includes maps that purport to show the ratio of drug and alcohol usage from state to state. Rhode Island leads the nation in the use of illicit drugs, with 11.2 percent of respondents over the age of 12 reporting drug use in the past month. At the other end of the scale, a scant 5.7 percent of North Dakotans used drugs in an average month, according to numbers extracted from the 2005-2006 National Survey on Drug Use and Health conducted by the Department of Health and Human Services.

The figures and explanatory text are from SAMHSA, Office of Applied Studies, National Survey on Drug Use and Health.

Marijuana Withdrawal Rivals Nicotine

Kicking pot or cigarettes leads to anxiety, sleep problems.

A small study in the journal Alcohol and Drug Dependence likened withdrawal from cannabis to that of withdrawal from nicotine, in the case of smokers addicted to either or both substances. The study gave further support to the growing body of evidence supporting the existence of a clinically significant marijuana withdrawal syndrome in heavy marijuana smokers.

As one cigarette smoker in withdrawal famously put it, “I cannot think, cannot concentrate, cannot remember.” Now it appears that heavy marijuana smokers who go cold turkey might be susceptible to the same symptoms of withdrawal from addiction.

Dr. Ryan Vandrey, a professor of psychiatry at Johns Hopkins School of Medicine, and principle author of the study, told Amy Norton of Reuters Health that marijuana withdrawal can cause symptoms similar to nicotine withdrawal, such as anxiety, irritability, difficulty concentrating, and sleep problems. Marijuana withdrawal, which typically affects only heavy smokers, has not been well studied or characterized in the scientific community. Some marijuana advocates view the idea of marijuana withdrawal with considerable skepticism. “These new findings give some idea of its significance,” Vandrey said, and will help inform heavy pot smokers about the symptoms they may face if they abruptly stop smoking.

In the journal article, “A within-subject comparison of withdrawal symptoms during abstinence from cannabis, tobacco, and both substances,” Vandrey and his co-authors conclude: “Overall withdrawal severity associated with cannabis alone and tobacco alone was of a similar magnitude. Withdrawal during simultaneous cessation of both substances was more severe than for each substance alone, but these differences were of short duration and substantial individual differences were noted.”

The authors argue that “cannabis withdrawal is clinically important and warrants detailed description in the DSM-V and ICD-11.” The DSM-V and the ICD-11 are standardized diagnostic classification systems used in the practice of psychiatry.

Participants in the study smoked marijuana at least four times a day, and cigarette smokers consumed 20 or more cigarettes daily.

Since, as Vandrey notes, the presence of withdrawal symptoms often leads to failure when smokers are attempting to quit, it is possible that many more people are trying—and failing—to quit marijuana than researchers have previously suspected. Dr. Vandrey suggested that since difficulty sleeping is one common symptom of withdrawal, sleep medications might be indicated in the case of severe marijuana withdrawal, but cautioned that more study is needed.

Along with insomnia and anxiety, heavy marijuana smokers often report an increase in the frequency and vividness of their dreams during withdrawal as well.

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See also: Marijuana Withdrawal nicotine