NIDA’s Dark View of Teen Marijuana Use

Federal study also discusses medical marijuana.

Considering the impasse on marijuana policy between state and federal governments in the U.S., the primary government agency in charge of drug research—NIDA, the National Institute on Drug Abuse—would seem to be caught between a rock and a hard place. Neuroscientists and other marijuana investigators who do research under NIDA grants have a fine line to walk in their efforts to disseminate research findings on cannabis.

From a public health point of view, NIDA is expected to keep up the pressure against drug legalization, or at least keep out of the fight, while also researching the medical pros and cons of cannabis. So it was with some interest that drug policy officials took in a recent article in the New England Journal of Medicine by NIDA director Nora Volkow titled “Adverse Health Effects of Marijuana Use.”

While the press has understandably centered on the risk of marijuana use among teens, which is the focus of the study, the report also contains some surprising admissions about marijuana’s health benefits as well as its addictive potential.

The teen risk emphasis comes from recent studies on two fronts—impaired driving and impaired brain function. The first is seriously confounded by dual use with alcohol, and the second is based, at least in part, on a controversial long-term study showing that marijuana use in the early years demonstrably lowers adult IQs.

No one would suggest that heavy marijuana smoking is good for developing teen brains, and there is sufficient evidence to worry about impairment to memory and to certain so-called “executive” cognitive functions. It is not clear how lasting these effects can be, but lead author Volkow is confident enough to say in a prepared statement that “Physicians in particular can play a role in conveying to families that early marijuana use can interfere with crucial social and developmental milestones and can impair cognitive development.” 

That these negative effects can be the outcome of heavy pot smoking in the teen years seems established beyond reasonable doubt. The extent and duration of these negative outcomes remain the topic of vociferous debate—although it is increasingly clear that the body’s endogenous cannabinoid system plays a key role in synapse formation during early brain development.

Meanwhile, the report re-emphasized the fact that marijuana is an addictive drug for some users—a fact that should not need re-emphasizing, but, lamentably, does. As Volkow and her co-authors write: “The evidence clearly indicates that long-term marijuana use can lead to addiction. Indeed, approximately 9% of those who experiment with marijuana will become addicted.”

Moreover, as regular readers of Addiction Inbox already know, “there is also recognition of a bona fide cannabis withdrawal syndrome (with symptoms that include irritability, sleeping difficulties, dysphoria, craving, and anxiety), which makes cessation difficult and contributes to relapse.” And, in line with the report’s overall theme, “those who begin in adolescence are approximately 2 to 4 times as likely to have symptoms of cannabis dependence within 2 years after first use.”

To their credit, the investigators decline to endorse the claim that marijuana use exacerbates or initiates episodes of illness in patients with schizophrenia and other psychoses, noting that “it is inherently difficult to establish causality in these types of studies because factors other than marijuana use may be directly associated with the risk of mental illness.” Furthermore, while early marijuana use is associated with an increased risk of dropping out of school, “reports of shared environmental factors that influence the risks of using cannabis at a young age and dropping out of school suggest that the relationship may be more complex…. The relationship between cannabis use by young people and psychosocial harm is likely to be multifaceted, which may explain the inconsistencies among studies.”

Indeed. The report also declares that the effects of long-term pot smoking on the risk of lung cancer are “unclear,” and that “the smoking of cigarettes containing both marijuana and tobacco products is a potential confounding factor with a prevalence that varies dramatically among countries.”

In conclusion, the strict demands of causality mean that the long-term effect of chronic marijuana exposure is not known with any certainty. It is possible, even likely, that these effects can vary dramatically from one smoker to another. But the equally persuasive demands of common sense dictate that inhaling dried, super-heated vegetable matter on a regular basis is likely to degrade your health, the more so if you are young and healthy to begin with.

As for other health issues: “The authoritative report by the Institute of Medicine, Marijuana and Medicine, acknowledges the potential benefits of smoking marijuana in stimulating appetite, particularly in patients with the acquired immunodeficiency syndrome (AIDS) and the related wasting syndrome, and in combating chemotherapy-induced nausea and vomiting, severe pain, and some forms of spasticity. The report also indicates that there is some evidence for the benefit of using marijuana to decrease intraocular pressure in the treatment of glaucoma.”

A detailed section titled “Clinical Conditions with Symptoms That May Be Relieved by Treatment with Marijuana or other Cannabinoids” brought additional research to light:

—Glaucoma: “More research is needed to establish whether molecules that modulate the endocannabinoid system may not only reduce intraocular pressure but also provide a neuroprotective benefit in patients with glaucoma.”

—Nausea: “THC is an effective antiemetic agent in patients undergoing chemotherapy, but patients often state that marijuana is more effective in suppressing nausea…. Paradoxically, increased vomiting (hyperemesis) has been reported with repeated marijuana use. [See various blog posts by Drugmonkey and me, starting with this and this.]

—AIDS-associated conditions: “Smoked or ingested cannabis improves appetite and leads to weight gain and improved mood and quality of life among patients with AIDS.”

—Chronic pain: “Studies have shown that cannabinoids acting through central CB1 receptors, and possibly peripheral CB1 and CB2 receptors, play important roles in… various models of pain. These findings are consistent with reports that marijuana may be effective in ameliorating neuropathic pain, even at very low levels of THC.”

—Inflammation: “Cannabinoids (e.g., THC and cannabidiol) have substantial anti-inflammatory effects…. Animal models have shown that cannabidiol is a promising candidate for the treatment of rheumatoid arthritis and for inflammatory diseases of the gastrointestinal tract (e.g., ulcerative colitis and Crohn’s disease).”

—Multiple sclerosis: “Nabiximols (Sativex, GW Pharmaceuticals), an oromucosal spray that delivers a mix of THC and cannabidiol, appears to be an effective treatment for neuropathic pain, disturbed sleep, and spasticity in patients with multiple sclerosis. Sativex… is currently being reviewed in phase 3 trials in the United States in order to gain approval from the Food and Drug Administration.”

—Epilepsy: In a recent small survey of parents who use marijuana with a high cannabidiol content to treat epileptic seizures in their children, 11% reported completed freedom from seizures…. Although such reports are promising, insufficient safety and efficacy data are available on the use of cannabis botanical for the treatment of epilepsy. However, there is increasing evidence of the role of cannabidiol as an antiepileptic agent in animal models.”

Volkow N.D., Baler R.D., Compton W.M. & Weiss S.R.B.  Adverse health effects of marijuana use., The New England journal of medicine,    PMID: 24897085

Drug Links, Various

Pharmacology, Politics, and Recovery

* USA Today article on Opana abuse rivalling Oxy abuse.

* US Attorneys Crack Down on California Medical Marijuana Dispensaries.

* Downloadable reports from Alcohol Justice, an industry watchdog group.

* With regard to the approval of Lorcaserin as a diet pill, here's the saga of Phen-Fen--how a blockbuster diet pill died.

* Why the Dutch "weed pass" won't work.

* Cigars won't save you: Cigars cause your body similar problems as cigarettes.

* Playwright Sam Shepard on his stint in rehab: “I finally did AA down on Pico Boulevard. I said, 'Don’t put me in with Elton John or anything, just throw me to the lions.’”

* 4,848 and 390: number of medical marijuana providers in Montana in March 2011 and June 2012, respectively.

* Andrea Mitchell talks to NIDA's Nora Volkow

* Listen to the talking urinal cake: Don’t drive drunk

* Feds say celebrity psychiatrist Dr. Drew was paid by Glaxo to talk up antidepressant on TV.

* Reactions to Marc Ambinder's GQ piece on Obama and the Drug War

* Lengthy interview with Drug Czar Kerlikowske by Mike Guy at The Fix:


Graphics Credit: http://tucsonvelo.com

Random Notes from the College on Problems of Drug Dependence

Opening day addresses at the annual meeting.

(These are notes on research in progress, not findings written in stone).

--NIDA director Nora Volkow talked up buspirone (Buspar) as a treatment for cocaine addiction, and referred to favorable results on buspirone for cocaine self-administration in monkeys in a large clinical trial. Also, different vaccine strategies are in the works, including different pharmacological approaches to blocking specific dopamine transporter molecules.

--Edward Sellers of DL Global Partners, a drug research consulting firm, emphasized the importance of enzyme variations in smoking. Variants of the CYP2A6 enzyme of metabolization allow us to identify “slow metabolizers” who respond well to placebo or nicotine patch therapy, and other smokers who don’t.

--Sherry McKee of the Yale University School of Medicine reminded everyone that cigarette smokers—even very light smoking “chippers”— are far more likely to have concurrent drinking problems than non-smokers. Smoking helps drinkers drink more and longer. To demonstrate such “potentiated reinforcement,” she showed a delightful video of her child eating cookies, then craving a glass of milk, then succumbing to another round of cookie consumption…

--Jack Henningfield of Pinney Associates, and former NIDA research chief, said that the reason the National Institute on Alcohol Abuse and Alcoholism (NIAAA) became an agency focused on “one molecule” is because Senator Harold Hughes, recovering alcoholic from Iowa, and Bill W., co-founder of Alcoholics Anonymous, wanted it that way.

--David Penetar of Harvard Medical School and McLean Hospital added more evidence of the link between alcohol and cigarettes, noting that “90 per cent of smokers drink,” and that smokers are three times as likely to be alcoholics than non-smokers. He pointed to research documenting a disturbing “increased desire to drink” when wearing a nicotine patch. With a patch, subjects reported feeling the effects of alcohol sooner and longer.

Photo Credit: http://www.thejournalshop.com/

NIH Turf Wars

Combining Addiction Agencies.

For nearly a decade, the idea of combining the federal government’s two primary addiction research institutes has made good sense. Recently, an independent panel officially recommended a merger—but alcohol researchers opposed the notion, as they have in the past.

The National Institutes of Health, the nation’s premier biological research institution, is composed of 27 separate medical institutes, each fighting for its share of funding and recognition under the larger umbrella of the parent organization. If this seems like an unwieldy arrangement, that’s because it is. Duplication and overlap is inevitable in as vast an enterprise as the NIH. Yet the arrangement has produced some of the best medical and biological research in the world.

Former NIH director Harold Varmus complained, according to ScienceInsider (Sub req) “that the sprawl hobbles NIH’s ability to respond to new science.” The most obvious case for streamlining and cost-savings has always been the National Institute on Drug Abuse (NIDA) on the one hand, and the clumsily named National Institute on Alcohol Abuse and Alcoholism (NIAAA) on the other.

In 2006, Congress told the NIH to create the Scientific Management Review Board to recommend ways of overhauling the NIH structure. The obvious place to start was with the two overlapping addiction institutes.

It was not a new idea. In 2003, the National Academy of Sciences (NAS) recommended merging the agencies due to “overlapping missions.” Enoch Gordis, then director of the NIAAA, was adamantly opposed to the idea, and the undertaking fell away.

Recently, the Scientific Management Review Board of the NIH voted 12-3 in favor of the merger, and sent the proposal to the desk of NIH director Francis Collins. However, the board also recommended an outside search for a director, thereby eliminating current NIDA director Norah Volkow from consideration. Dr. Volkow has been an active and public advocate for addiction awareness. An obvious choice to head the combined institute, provisionally known as the National Institute on Addiction, she would be a significant loss to the NIH. A spokesperson for Dr. Volkow would only offer NIDA’s official stance on the matter: “NIDA’s position has always been that we should create an organizational structure that best serves the science of addiction. We appreciate the thoughtful process that preceded the Board’s recommendation, and we look forward to hearing about a final decision soon.”

For years, NIAAA supporters had a ready answer when asked what made their agency different from NIDA: the liver. NIAAA did research on the liver and other organs and metabolic processes involved in metabolizing alcohol. But over the past two decades, the meaningful research coming out of NIDA has been the primary focus for most addiction researchers. NIDA’s forceful and forward-thinking director, Norah Volkow, followed an equally outspoken director, Alan Leshner. At NIAAA, the most recent director, Dr. T.K. Li, came to the institute after a distinguished career as an alcohol researcher at the University of Indiana. Dr. Li recently retired and the position is being filled on an interim basis by acting director Kenneth Warren.

NIAAA has always been the weaker sister in the addiction research family. With only half of NIDA’s billion-dollar budget, NIAAA deals strictly with alcohol research, even if the NIAAA has at times seemed unsure of what constitutes its main area of study—alcohol the addictive drug, or alcohol the healthy beverage. The merger would represent a recognition that alcohol is just another drug, albeit a legal one.

However, in a Science (sub req) interview, Francis Collins, the current director of the NIH, noted that the advisory board was “not able to come to a consensus” on the NIDA-NIAAA merger. “I guess most people would have said, ‘Well yeah, of course.’ But when you look at the details…. and you consider that alcohol is after all a legal substance and 90% of us at some point in our lives are comfortable with taking it in while the drug abuse institute is largely focused on drugs that are not legal. So there's a personality of the institute issue here that people thought might be important to preserve, others thought would be good not to preserve.”

The director’s remarks reflect the turf protection responses that this seemingly straightforward move invokes. An article by Bob Curley at Join Together notes that last year, the advisory board “voted unanimously in favor of studying the merger despite the fact that every group and individual testifying live at the hearing opposed combining the two agencies.”

Every group and individual? Curley quotes Lawrence Tabak, former acting deputy director of NIH, who minimized the likelihood of significant cost savings, and said, “there are also some issues that NIAAA deals with that are not ‘addictive’ in nature, such as binge drinking.” Representatives from the Research Society on Alcoholism and the American Association for the Study of Liver Diseases said that NIAAA’s harm reduction approach to alcohol use was “fundamentally at odds with NIDA’s focus on illegal drugs.” The National Association of Addiction Treatment Providers also opposed the merger, citing fears of a “loss of focus” on the problems unique to alcohol.

Beyond the official testimony, many prominent drug addiction experts feel differently. “The basic biology of drug abuse and addiction are highly overlapping for all drugs of abuse,” according to Eric Nestler of the department of neuroscience at the Mount Sinai School of Medicine. “There’s a huge confusion—not only among the lay public but among some treatment providers too—that alcohol is ‘not a drug,’” he said in the Join Together article. “This is absurd, yet the current separation of alcohol into a separate institute provides credence to that notion.”

According to noted addiction researcher Charles O’Brien of the University of Pennsylvania’s department of psychiatry, “There’s no scientific rationale to have a separate institute for a single drug. Ethanol activates the reward system similar to opioids and other abused drugs using different mechanisms to act on the same structures.” In addition, O’Brien notes that most addicts use more than one drug, but that NIAAA funding limit researchers to projects for “pure alcoholics, despite the reality of the clinical populations.”

The dual agencies, by their very existence, imply that addiction to alcohol and addiction to other drugs are wholly separate spheres of inquiry and investigation—a notion damaging to scientific research and public health. The primary hurdle to the merger is political, not scientific.

On the face of it, the merger makes sense, and in fact is long overdue. To keep these agencies separate means continuing to perpetuate the myth that there is something crucial that separates alcoholism from drug addiction. And there isn’t. Treating alcoholism and alcohol abuse as a syndrome somehow apart from drug abuse and addiction is outdated and unwarranted. We know too much now about both conditions to maintain the pretense.

As DrugMonkey, a pseudonymous science blogger funded by the NIH, summed it up: “If Institutes are to be merged than NIDA/NIAAA is at the very top of the list. If these cannot be merged then I do not see how any other mergers can be accomplished.”

Graphics Credit: http://www.hbcprotocols.com/nihfunds.html

A Shot for Cigarette Addiction?

NIDA’s Nora Volkow on addiction vaccines.

Nora Volkow, director of the National Institute on Drug Abuse (NIDA), predicted in a telephone interview on Friday that a vaccine for cigarettes could be available in as little as three years, if two large ongoing Phase 3 trials—the last major FDA hurdle—prove as successful as earlier studies.

NicVax (Nicotine Conjugate Vaccine) from Nabi Biopharmaceuticals, with a boost from a $40 million up-front cash infusion from GlaxoSmithKline Biologicals SA, is poised to become the first of a new kind of science-based addiction treatment—an avenue of approach that brings with it great promise, and a significant number of problems.

I asked Dr. Volkow if the NicVax studies had shown evidence that the effects could be overcome with greater levels of smoking. This is a hurdle that has plagued early research on a promising cocaine vaccine, as reported in the Archives of General Psychiatry (See my post "Cocaine Vaccine Hits Snag").  In the cocaine studies, researchers found that users could overcome the blunting effects of cocaine antibodies by ingesting as much as ten times their normal level of cocaine—clearly a dangerous outcome that could enhance the possibility of lethal overdose.  (See discussions at Neurotopia  and DrugMonkey).

“I am very sensitive to that issue,” Volkow said during a conference call from NIDA's Eighth Annual Blending Conference in Albuquerque, NM, where she was a featured speaker. “But the data we have give no evidence that smokers increase their cigarettes to overcome the antibodies. It was that piece of the data that led me to approve funding.”

In fact, said Volkow, “craving decreased after these vaccinations, so we would not necessarily expect smokers to try to overcome the effects. We’ve also seen a dramatic decrease in cocaine administration in animal models.” The matter of defeating a vaccine by overindulging remains a theoretical rather than an established risk, Volkow believes. 

Vaccines may operate somewhat differently that we think, she explained, by helping to extinguish the conditioned responses to craving cues as well. “We did not expect to see [anti-craving effects],” she said. “Craving is a product of memory, associated stimuli, the anticipation of a pleasant response. With cigarettes, if you feel nothing, the brain mechanism of conditioning that drives craving starts to weaken.”

The vaccine itself “is not totally stopping all of the drug from getting into the brain. But it affects the pharmacological properties, so users don’t get the expected outcome.  Nobody knows exactly how this might accelerate the extinction process—we haven’t done the studies. It’s going to be intriguing to have a product that has the capacity to make extinction much more universal.”

Volkow admitted that “we need to get a wider response,” since a significant number of smokers and cocaine users do not form antibodies from the vaccines. In addition, “we need longer-lasting responses so we don’t have to re-vaccinate.” The cocaine vaccine under study is in Phase 2 trials, and it will be several years before more definitive results are in.

The Blending Conference Volkow was attending was titled “Blending Addiction Science and Practice: Evidence-Based Treatment and Prevention in Diverse Populations and Settings.” Despite her emphasis on science-based treatments, Volkow stated firmly that social intervention and psychological treatment can be equally important, and characterized the supposed line between physical addiction and psychological addiction as an “obsolete distinction.” It is important to remember, she said, that “psychosocial interventions make biological changes in the brain” as well.

“People are desperate, and vaccines will be very helpful to those who develop antibodies. People want these magic bullets, but we don’t yet know how these vaccines will effect the therapeutic landscape.”

Graphics Credit: http://www.attcnetwork.org/

Impulsivity and Addiction

The perils of a hypersensitive dopamine system.

The brooding, antisocial loner, the one with impulse control problems, a penchant for risk-taking, and a cigarette dangling from his lip, is a recognizable archetype in popular culture. From Marlon Brando to Bruce Lee, these flawed heroes are perhaps the ones with restless brain chemicals; the ones who never felt good and never knew why (“What are you rebelling against?” “What’ve you got?”).

A recent study at Vanderbilt University, published in Nature Neuroscience, used PET scans and fMRI imaging to suggest that impulsivity and other “antisocial” traits “predicted nucleus accumbens dopamine release and reward anticipation-related activity in response to pharmacological and monetary reinforcers, respectively.”

In other words, the Vanderbilt researchers maintained that so-called “psychopathic traits” like impulsivity and risk taking are linked to addiction and gambling by means of an overly active dopamine system. PET scans of dopamine responses to a low dose of amphetamine showed that “individuals who scored high on a personality assessment that teases out traits like egocentricity, manipulating others, and risk taking had a hypersensitive dopamine response system,” according to a press release from the National Institute on Drug Abuse (NIDA), which funded the study.

Putting a different spin on the matter, NIDA director Nora Volkow said: “By linking traits that suggest impulsivity and the potential for antisocial behavior to an overreactive dopamine system, this study helps explain why aggression may be as rewarding for some people as drugs are for others.”

Lead author Joshua Buckholtz of Vanderbilt said that “the amount of dopamine released was up to four times higher in people with high levels of these traits, compared to those who scored lower on the personality profile.  Buckholtz suggested that a pattern of exaggerated dopamine responses “could develop into psychopathic personality disorder.”

Dr. Robert Cloninger, a prominent addiction researcher, has asserted in the past that children who show a high propensity for risk-taking, along with impulsivity, or “novelty-seeking,” are more likely to develop alcoholism and other addictions later in life.

And, in interviews with the late psychologist Henri Begleiter for my book on addiction science, Begleiter insisted that addicts were stuck with a package of symptoms he called behavioral dysregulation. “Disinhibition, impulsivity, trouble fitting into society—you have certain behavioral disorders in kids who later develop into alcoholics and drug addicts,” he said. The behavior itself doesn’t cause the addiction. The dysregulated behavior is a symptom of the addiction.”

“When you talk to these people, as I have,” Begleiter said, “you see that the one thing they pretty much all report is that, under the influence of the drug, they feel much more normal. It normalizes their central nervous systems. Initially, what they have is a need to experience a normal life.”

So, it wasn’t ducktails, pool halls, tattoos, casual sex, or lack of parental involvement that caused addiction to alcohol and cigarettes and pot, and maybe cocaine and speed and heroin. It wasn’t just the “bad kids.” Irrational anger, impulsive decisions, certain compulsive behaviors like gambling—these behaviors were symptoms of the same group of related disorders that included drug and alcohol addiction, and which involved specific chemicals and areas of the brain related to reward, motivation, and memory.

The trait of impulsivity is a possible marker for addiction that may help explain why it is usually impossible to persuade addicts to give up their drugs by sheer force of logic—by arguing that the drugs will eventually ruin their health or kill them. “They tell me it’ll kill me,” sang Dave Van Ronk, “but they don’t say when.”

Consider the always-instructive case of cigarette smoking. In 1964, the Surgeon General’s Report on Smoking and Health laid out the case for the long-term ill effects of nicotine quite effectively—and millions of people quit smoking. A stubborn minority did not, and many of them still have not. Are they simply being hedonistic and irresponsible? Or are the long-term negative consequences, so dramatically clear to others, simply not capable of influencing their thinking to the same degree? Biochemical abnormalities similar to those predisposing certain people to addiction may also prevent them from comprehending the long-term results of their behavior.

Buckholtz, J., Treadway, M., Cowan, R., Woodward, N., Benning, S., Li, R., Ansari, M., Baldwin, R., Schwartzman, A., Shelby, E., Smith, C., Cole, D., Kessler, R., & Zald, D. (2010). Mesolimbic dopamine reward system hypersensitivity in individuals with psychopathic traits Nature Neuroscience, 13 (4), 419-421 DOI: 10.1038/nn.2510

Graphics Credit: http://www.nature.com/neuro/journal/

Q & A with Nora Volkow

NIDA director discusses cannabis, addiction vaccines, and gambling.

Recently, Addiction Inbox was offered the opportunity to submit questions to Nora Volkow, the director of the National Institute on Drug Abuse (NIDA). Dr. Volkow was kind enough to provide detailed answers by email. In her responses, she reveals a broad clinical understanding of addiction, and speculates on what this brain disorder might mean for “other diseases of addiction” like gambling.

Q: Clinical studies, like those by Barbara Mason at Scripps Institute, have documented a marijuana withdrawal syndrome among a minority of users. Are we prepared to say that marijuana is addictive? Why didn't we identify this syndrome years ago?

Nora Volkow: Absolutely, there is no doubt that some users can become addicted to marijuana. In fact, well over half of the close to 7 million Americans classified with dependence or abuse of an illicit drug are dependent on or abuse marijuana. It is important to clarify that while withdrawal is one of the criteria used to diagnose an addiction (which also includes compulsive use in spite of known adverse consequences), it is possible for an individual to suffer withdrawal symptoms without he or she being addicted to an abused substance.

Now, to answer your specific question, the reason for the relatively late realization that people who abuse marijuana can develop a cannabis withdrawal syndrome (CWS) if they try to quit is probably the result of at least two factors. First is the fact (which you hint at already) that a clinically relevant cannabis withdrawal syndrome may only be expected in a subgroup of cannabis-dependent patients. This may be partially explained by marijuana’s uptake into and slow release from fat cells, which can occur over days or weeks after last use. Thus, cessation of marijuana use may not be so abrupt, and could thereby diminish signs of withdrawal. The second factor relates to the small to negligible associations between recalled and prospectively assessed withdrawal symptoms, which may have precluded many previous, recall-based studies from detecting or properly characterizing CWS. It is also worth pointing out that other addictions (e.g., cocaine) were also not initially thought of as capable of triggering withdrawal symptoms.”

Q: Are there any anti-craving medications you are particularly excited about at this time?

Volkow: In the context of nicotine addiction, we have a host of nicotine replacement options as well as 2 medications that work through different mechanisms—all of which reduce craving and the risk of relapse during a cessation attempt, particularly when combined with some form of behavioral therapy. However, sustained abstinence from nicotine has been difficult to achieve, even with the current therapeutics that are available. So, at this point, I am very excited about a novel approach to the treatment of addiction—an approach that relies on vaccine development. Currently there are anti-nicotine vaccines in clinical testing, which are designed to capture the nicotine molecules while still in the bloodstream, thus blocking their entry in to the brain and inhibiting their behavioral effects. And while these vaccines were not intended specifically to reduce cravings, they appear to be effective in helping subjects who develop a high antibody response sustain abstinence over long periods of time. Even those people with a less robust antibody response to the vaccine, decreased their tobacco use. So this approach appears very promising.

Similarly, in the context of opiate addiction, we are very excited about the cumulative positive results of the clinical experience so far with buprenorphine, a long-acting partial agonist that acts on the same receptors as heroin and morphine, relieving drug cravings without producing the same intense "high" or dangerous side effects.

Q: You have suggested in the past that certain forms of overeating are addictions. There is good evidence for this. What about non-substance addictions, like gambling?

Volkow: The brain is composed of a finite number of circuits, for, for example, rewarding desirable experiences, remembering and learning about salient features and stimuli in the environment, developing emotional connections to other members of the social group, becoming aware of changes in interoceptive (internal) physiological states, etc. These and a few others are the circuits that the “world” acts upon. So it is almost by necessity that we’ll find significant overlaps in the circuits that mediate various forms of compulsive behaviors. We have yet to work out the details and the all important differences, but it stands to reason that there will be many manifestations of what we can call diseases of addiction. Thus, addiction to sex, gambling, alcohol, illicit drugs, shopping, video games, etc. all result from some degree of dysfunction in the ability of the brain to properly process what is salient, accurately predict and value reward, and inhibit emotional reactivity or deleterious behavior.

As we learn more about the significant overlaps at the genetic, neural, circuit, and systems levels we may be able to reap the benefits from complementary research into these various chemical and behavioral addictions.

Photo Credit: http://www.thechallenge.org

NIDA'S Updated Guide Book Emphasizes Science

Drug addiction treatment trends.

Favoring objective medicine over moral exhortation, the National Institute on Drug Abuse (NIDA) has updated one of its primary research guides, continuing the trend toward focusing on the scientific aspects of drug and alcohol addiction.

In the preface to the updated 2nd Edition of Principles of Drug Addiction Treatment, available here, NIDA Director Nora D. Volkow writes:

“Addiction affects multiple brain circuits, including those involved in reward and motivation, learning and memory, and inhibitory control over behavior. Some individuals are more vulnerable than others to becoming addicted, depending on genetic makeup, age of exposure to drugs, other environmental influences, and the interplay of all these factors.”

Looking toward the future, Volkow writes that “we will harness new research results on the influence of genetics and environment on gene function and expression (i.e., epigenetics), which are heralding the development of personalized treatment interventions.”

Here are excerpts from a section of the updated guide titled “Principles of Effective Treatment.”

--No single treatment is appropriate for everyone.

“Matching treatment settings, interventions, and services to an individual's particular problems and needs is critical to his or her ultimate success in returning to productive functioning in the family, workplace, and society.”

--Treatment needs to be readily available.

“Potential patients can be lost if treatment is not immediately available or readily accessible. As with other chronic diseases, the earlier treatment is offered in the disease process, the greater the likelihood of positive outcomes.”

-- Remaining in treatment for an adequate period of time is critical.

“Research indicates that most addicted individuals need at least 3 months in treatment to significantly reduce or stop their drug use and that the best outcomes occur with longer durations of treatment. Recovery from drug addiction is a longterm process and frequently requires multiple episodes of treatment.”

-- Medications are an important element of treatment for many patients, especially when combined with counseling and other behavioral therapies.

“For example, methadone and buprenorphine are effective in helping individuals addicted to heroin or other opioids stabilize their lives and reduce their illicit drug use. Naltrexone is also an effective medication for some opioid-addicted individuals and some patients with alcohol dependence. Other medications for alcohol dependence include acamprosate, disulfiram, and topiramate.”

-- Many drug-addicted individuals also have other mental disorders.

“Because drug abuse and addiction—both of which are mental disorders—often co-occur with other mental illnesses, patients presenting with one condition should be assessed for the other(s). And when these problems co-occur, treatment should address both (or all), including the use of medications as appropriate.”

-- Treatment programs should assess patients for the presence of HIV/ AIDS, hepatitis B and C, tuberculosis, and other infectious diseases as well as provide targeted risk-reduction counseling to help patients modify or change behaviors that place them at risk of contracting or spreading infectious diseases.

“Typically, drug abuse treatment addresses some of the drug-related behaviors that put people at risk of infectious diseases. Targeted counseling specifically focused on reducing infectious disease risk can help patients further reduce or avoid substance-related and other high-risk behaviors.”

Graphics Credit: NIDA