MDMA Likes It Hot

X and ambient air temperature.

One of the enduring mysteries about MDMA, the popular amphetamine derivative known as Ecstasy, or X, is the relationship between the drug and ambient air temperature. Why are raves hot, sweaty, and full of loud music and flashing lights? Because “human subjects report a higher euphoric state when taking the drug in sensory rich environments,” according to researchers. So there’s a reason for all those glow sticks and speaker stacks. But is it something inherent in the mechanism of the drug—or simply the overheated party atmosphere combined with vigorous dancing—that can sometimes raise a ravers’ body temperature to dangerous levels?

Drug researchers have known for some time that Ecstasy and high temperature are somehow interlinked. Animal studies have produced strong evidence that a heated environment can cause an increase in MDMA-stimulated serotonin 5-HT response. Many ravers take steps to prevent hyperthermia, or overheating, by regularly drinking water and coming off the dance floor at regular intervals. Most people have heard of hypothermia, a condition in which body temperature drops to dangerously low levels. But hyperthermia can be just as deadly, and it is a common emergency room complaint in MDMA admissions. 

In animal models, rats on MDMA (they like it enough to self-administer) show significantly elevated responses to serotonin in the nucleus accumbens at high room temperatures. What does that mean? What goes up must come down: It opens the door to possible serotonin depletion, which can cause dysfunctions in mood and cognition. Researchers at the University of Texas in Austin have found that in rodents, “the magnitude of the hyperthermic response has been tightly correlated with MDMA-induced 5-HT depletion in various brain regions.” The question they pose is whether “elevated ambient temperatures, such as those encountered in rave venues, can exacerbate MDMA-induced temperature-increasing effects and the likelihood of adverse drug effects.” (Cocaine has temperature-related effects as well. When the ambient air temperature is higher than 75 degrees F, accidental cocaine overdoses increase.)

Ecstasy boosts dopamine as well. The Texas researchers suggest that “the combined enhancement of 5-HT and dopamine may contribute to MDMA’s unique effects on thermoregulation.” They also found that core temperature responses appeared to be “experience-dependent,” meaning that rats didn’t show significantly elevated core temperatures in warm rooms until after they had rolled with MDMA at least ten times. And the worse it gets, the worse it gets, according to the report, published in European Neuropsychopharmacology: “Our results suggest that a heated environment facilitates MDMA-induced disruption of homeostatic thermoregulatory responses, but that repeated exposure to MDMA may also disrupt thermoregulation regardless of ambient temperature.”

So, while all that sweaty dancing amps up the perceptual effects of Ecstasy, it isn’t necessarily implicated in overheating. To simulate a nightclub full of X-ed out ravers, investigators at the Scripps Research Institute tested rats on MDMA while the animals exercised on activity wheels.  Writing in Pharmacology Biochemistry and Behavior, the researchers found that “wheel activity did not modify the hyperthermia produced…. These results suggest that nightclub dancing in the human Ecstasy consumer may not be a significant factor in medical emergencies.”

Bottom line: Although we have a reasonable idea of how it works in animals, we don’t really know how much of that knowledge applies to humans in rave settings. Research aimed at teasing out the specifics of temperature-related responses to MDMA is ongoing. And it does matter. Frequent heat-induced responses could lead to prolonged 5-HT depletion, which is suspected of causing an escalation of drug intake in experienced Ecstasy users. And frequent, escalating use of MDMA is implicated in a long roster of potential cognitive impairments. 

Photo Credit: http://electricchildren.com

The Mysteries of the Blunt

Why do so many smokers combine tobacco with marijuana?

People who smoke a combination of tobacco and marijuana, a common practice overseas for years, and increasingly popular here in the form of “blunts,” may be reacting to some unidentified mechanism that links the two drugs. Researchers believe such smokers would be well advised to consider giving up both drugs at once, rather than one at a time, according to an upcoming study in the journal Addiction.

Clinical trials of adults with cannabis use disorders suggest that “approximately 50% are current tobacco smokers,” according to the report, which was authored by Arpana Agrawal and Michael T. Lynskey of Washington University School of Medicine, and Alan J. Budney of the University of Arkansas for Medical Sciences.  “As many cannabis users smoke a mixture of cannabis and tobacco or chase cannabis use with tobacco, and as conditioned cues associated with smoking both substances may trigger use of either substance,” the researchers conclude, “a simultaneous cessation approach with cannabis and tobacco may be most beneficial.”

A blunt is simply a marijuana cigar, with the wrapping paper made of tobacco and the majority of loose tobacco removed and replaced with marijuana. In Europe, smokers commonly mix the two substances together and roll the combination into a single joint, the precise ratio of cannabis and nicotine varying with the desires of the user. “There is accumulating evidence that some mechanisms linking cannabis and tobacco use are distinct from those contributing to co-occurring use of drugs in general,” the investigators say. Or, as psychiatry postdoc Erica Peters of Yale put it in a press release, “There’s something about tobacco use that seems to worsen marijuana use in some way.” The researchers believe that this “something” involved may be a genetic predisposition. In addition to an overall genetic proclivity for addiction, do dual smokers inherit a specific propensity for smoked substances? We don’t know—but evidence is weak and contradictory so far.

Wouldn’t it be easier to quit just one drug, using the other as a crutch? The researchers don’t think so, and here’s why: In the few studies available, for every dually addicted participant who reported greater aggression, anger, and irritability with simultaneous cessation, “comparable numbers of participants rated withdrawal associated with dual abstinence as less severe than withdrawal from either drug alone.” So, for dual abusers, some of them may have better luck if they quit marijuana and cigarettes at the same time. The authors suggest that “absence of smoking cues when abstaining from both substances may reduce withdrawal severity in some individuals.” In other words, revisiting the route of administration, a.k.a. smoking, may trigger cravings for the drug you’re trying to quit. This form of “respiratory adaption” may work in other ways. For instance, the authors note that, “in addition to flavorants, cigarettes typically contain compounds (e.g. salicylates) that have anti-inflammatory and anesthetic effects which may facilitate cannabis inhalation.”

Studies of teens diagnosed with cannabis use disorder have shown that continued tobacco used is associated with a poor cannabis abstention rate. But there are fewer studies suggesting the reverse—that cigarette smokers fair poorly in quitting if they persist in cannabis use. No one really knows, and dual users will have to find out for themselves which categories seems to best suit them when it comes time to deal with quitting.

We will pass up the opportunity to examine the genetic research in detail. Suffice to say that while marijuana addiction probably has a genetic component like other addictions, genetic studies have not identified any gene variants as strong candidates thus far. The case is stronger for cigarettes, but to date no genetic mechanisms have been uncovered that definitively show a neurobiological pathway that directly connects the two addictions.

There are all sorts of environmental factors too, of course. Peer influences are often cited, but those influences often seem tautological: Drug-using teens are members of the drug-using teens group. Tobacco users report earlier opportunities to use cannabis, which might have an effect, if anybody knew how and why it happens.

Further complicating matters is the fact that withdrawal from nicotine and withdrawal from marijuana share a number of similarities.  The researchers state that “similar withdrawal syndromes, with many symptoms in common, may have important treatment implications.” As the authors sum it up, cannabis withdrawal consists of “anger, aggression or irritability, nervousness or anxiety, sleep difficulties, decreased appetite or weight loss, psychomotor agitation or restlessness, depressed mood, and less commonly, physical symptoms such as stomach pain and shakes/tremors.” Others complain of night sweats and temperature sensitivity.

And the symptoms of nicotine withdrawal? In essence, the same. The difference, say the authors, is that cannabis withdrawal tends to produce more irritability and decreased appetite, while tobacco withdrawal brings on an appetite increase and more immediate, sustained craving. Otherwise, the similarities far outnumber the differences.

None of this, however, has been reflected in the structure of treatment programs: “Emerging evidence suggests that dual abstinence may predict better cessation outcomes, yet empirically researched treatments tailored for co-occurring use are lacking.”

The truth is, we don’t really know for certain why many smokers prefer to consume tobacco and marijuana in combination. But we do know several reasons why it’s not a good idea. Many of the health-related harms are similar, and presumably cumulative: chronic bronchitis, wheezing, morning sputum, coughing—smokers know the drill. Another study cited by the authors found that dual smokers reported smoking as many cigarettes as those who only smoked tobacco. All of this can lead to “considerable elevation in odds of respiratory distress indicators and reduced lung functioning in those who used both.” However, there is no strong link at present between marijuana smoking and lung cancer.

Some researchers believe that receptor cross-talk allows cannabis to modify receptors for nicotine, or vice versa. Genes involved in drug metabolism might somehow predispose a subset of addicts to prefer smoking. But at present, there are no solid genetic or environmental influences consistent enough to account for a specific linkage between marijuana addiction and nicotine addiction, or a specific genetic proclivity for smoking as a means of drug administration.

Agrawal, A., Budney, A., & Lynskey, M. (2012). The Co-occurring Use and Misuse of Cannabis and Tobacco: A Review Addiction DOI: 10.1111/j.1360-0443.2012.03837.x

Photo credit:  http://stuffstonerslike.com

“Bath Salts” and Ecstasy Implicated in Kidney Injuries

“A potentially life-threatening situation.”

Earlier this month, state officials became alarmed by a cluster of puzzling health problems that had suddenly popped up in Casper, Wyoming, population 55,000. Three young people had been hospitalized with kidney injuries, and dozens of others were allegedly suffering from vomiting and back pain after smoking or snorting an herbal product sold as “blueberry spice.” The Poison Review reported that the outbreak was presently under investigation by state medical officials.  “At this point we are viewing use of this drug as a potentially life-threatening situation,” said Tracy Murphy, Wyoming state epidemiologist.

It is beginning to look like acute kidney injury from the newer synthetic drugs may be a genuine threat. And if that wasn’t bad enough, continuing research has implicated MDMA, better known as Ecstasy, as another potential source of kidney damage. Recreational druggies, forewarned is forearmed.

Bath salts first. In the Wyoming case, while the drug in question may have been one of the synthetic marijuana products marketed as Spice, it’s entirely possible that the drug in question was actually one or more of the new synthetic stimulants called bath salts. (Quality control and truth in packaging are not part of this industry). The American Journal of Kidney Diseases recently published a report titled “Recurrent Acute Kidney Injury Following Bath Salts Intoxication.” It features a case history that Yale researchers believe to be “the first report of recurrent acute kidney injury associated with repeated bath salts intoxication.”  The most common causes for emergency room admissions due to bath salts—primarily the drugs MDPV and mephedrone—are agitation, hallucinations, and tachycardia, the authors report. But the case report of a 26-year old man showed recurrent kidney injury after using bath salts. The authors speculate that the damage resulted from “severe renal vasospasm induced by these vasoactive substances.” (A vasoactive substance can constrict or dilate blood vessels.)

A possible secondary mechanism of action for kidney damage among bath salt users is rhabdomyolysis—a breakdown of muscle fibers that releases muscle fiber contents into the bloodstream, causing severe kidney damage. Heavy alcohol and drug use, especially cocaine, are also known risk factors for this condition. The complicating factor here is that rhabdomyolysis has also been described in cases of MDMA intoxication, and here we arrived at the second part of the story.

In 2008, the Clinical Journal of the American Society of Nephrology published “The Agony of Ecstasy: MDMA and the Kidney.” In this study, Garland A. Campbell and Mitchell H. Rosner of the University of Virginia Department of Medicine found that “Ecstasy has been associated with acute kidney injury that is most commonly secondary to nontraumatic rhabdomyolysis but also has been reported in the setting of drug-induced liver failure and drug-induced vasculitis.”

Chemically, MDMA is another amphetamine spinoff, like mephedrone and other bath salts. Many people take this club drug regularly without apparent harm, whereas others seem to be acutely sensitive and can experience serious toxicity, possibly due to genetic variance in the breakdown enzyme CYP2D6. The authors trace the first case report of acute kidney injury due to Ecstasy back to 1992, but “because most of these data are accrued from case reports, the absolute incidence of this complication cannot be determined.” 

 Campbell and Rosner believe that nontraumatic rhabdomyolysis is a likely culprit in many cases, and speculate that the condition is “greatly compounded by the ambient temperature, which in crowded rave parties is usually elevated.” If a physician suspects rhabdomyolysis in an Ecstasy user, “aggressive cooling measures should be undertaken to lower the patient’s core temperature to levels that will lessen further muscle and end-organ injury.” This complication can have far-reaching effects: The authors note the case history of “transplant graft loss of both kidneys obtained from a donor with a history of recent Ecstasy use.”

In addition, there may be undocumented risks to the liver as well. An earlier study by Andreu et. al. claims that “up to 31% of all drug toxicity-related acute hepatic failure is due to MDMA… Patients with severe acute hepatic failure secondary to ecstasy use often survive with supportive care and have successfully undergone liver transplantation.” 

But the picture is far from clear: “Unfortunately, no case reports of acute kidney injury secondary to ecstasy have had renal biopsies performed to allow for further elucidation…” And attributing firm causation is difficult, due to the fact that MDMA users often use other drugs in combination, some of which, like cocaine, can cause kidney problem all by themselves.

A study by Harold Kalant of the University of Toronto’s Addiction Research Foundation, published in the Canadian Medical Association Journal, proposed that “dantrolene, which is a drug used to stop the intense muscle contractures in malignant hyperthermia, should also be useful in the hyperthermic type of MDMA toxicity. Numerous cases have now been treated in this way, some with rapid and dramatic results even when the clinical picture suggested the likelihood of a fatal outcome.”

Adebamiro, A., and Perazella, M. (2012). Recurrent Acute Kidney Injury Following Bath Salts Intoxication American Journal of Kidney Diseases, 59 (2), 273-275 DOI: 10.1053/j.ajkd.2011.10.012

Graphics Credit:  http://trialx.com  

LSD and Alcohol: The History

Back when acid was legal.

After last week’s blitz of coverage concerning studies done in the 60s on the use of LSD for the treatment of alcoholism, I thought it would be useful to provide a bit of background; some pertinent psychedelic history to help put this information in perspective:

It may come as a surprise to many people that throughout the 60s, there were LSD clinics operating in England and Europe. European LSD therapists tended to use very low doses as an adjunct to traditional psychoanalytic techniques. But North American researchers took a different, bolder approach. When “psychedelic” therapy began to catch on in Canada and the United States, therapists typically gave patients only one or two sessions at very high doses. These early efforts were aimed at producing spontaneous breakthroughs or recoveries in alcoholics through some manner of religious epiphany or inner conversion experience. The only other quasi-medical approach of the day, the Schick Treatment Center’s brand of “aversion therapy,” was not seen to produce very compelling long-term recovery rates, and subsequently fell out of favor. In this light, the early successes with LSD therapy, sometimes claimed to be in the 50-75 per cent range, looked noteworthy indeed. However, the design and criteria of the LSD/alcoholism studies varied so widely that it has never been possible to draw definitive conclusions about the work that was done, except to say that LSD therapy seemed to be strikingly effective for certain alcoholics. Some patients were claiming that two or three trips on LSD were worth years of conventional psychotherapy—a claim not heard again until the advent of Prozac thirty years later.

 “I’ve taken lysergic acid several times, and have collected considerable information about it,” Bill Wilson, the co-founder of Alcoholics Anonymous, disclosed in a private letter written in 1958. “At the moment, it can only be used for research purposes. It would certainly be a huge misfortune if it ever got loose in the general public without a careful preparation as to what the drug is and what the meaning of its effects may be.”  Like many others, Wilson was excited by LSD’s potential as a treatment for chronic alcoholism. Even Hollywood was hip to the new therapy. Cary Grant, among others, took LSD under psychiatric supervision and pronounced it immensely helpful as a tool for psychological insight. Andre Previn, Jack Nicholson, and James Coburn agreed. (It could be argued that the human potential movement began here).

No drug this powerful and strange, if American history was any guide, could remain legal for long. Unlike their colleagues in the intelligence agencies, politicians and law enforcement officers didn’t know about Mongolian shamans and their fly agaric mushrooms; about European witches and their use of psychoactive plant drugs like nightshade and henbane; about Persian sheiks with their cannabis water pipes; Latin American brujos with their magic vines.

But for the CIA, the big fish was always LSD.

What interested the Central Intelligence Agency about LSD was its apparent ability to produce the symptoms of acute psychosis. Operation ARTICHOKE was designed to ferret out LSD’s usefulness as an instrument of psychological torture, and as a possible means of destabilizing enemy forces by means of aerosol sprays or contaminated water supplies. (The drug’s overwhelming potency made such parts-per-billion fantasies a possibility.)

The agency knew where to turn for a secure American source of supply. Eli Lilly and Co., the giant drug manufacturer, was already involved in LSD research on behalf of the U.S. government. The trouble was that LSD was expensive, and all roads led to Sandoz Laboratories in Switzerland. Organic LSD had to be painstakingly extracted from ergot, a fungus that grows in kernels of rye. Eventually, Sandoz and Eli Lilly successfully synthesized LSD in their own laboratories. With the advent of a reliable domestic supplier of synthetic LSD, the CIA under Allen Dulles was assured of a steady source for experimental purposes.

When LSD did not pan out as a reliable agent of interrogation, CIA investigators turned their attention to its purported ability to mimic acute psychosis—its “psychomimetic” aspect—which researchers were praising as a new avenue toward a biological understanding of schizophrenia. The CIA funneled grant money for LSD research into the academic and commercial R&D world through a host of conduits. Various experiments with non-consenting subjects—typically military or prison personnel—showed that LSD could sometimes break down established patterns of thought, creating a “twilight zone” during which the mind was more susceptible to various forms of psychological coercion and control. Perhaps, under the influence of LSD, prisoners could be transformed into counter-espionage agents. It also occurred to the CIA that the same drug could be used on their own agents for the same purposes. Numerous CIA agents took LSD trips in order to familiarize them with acid’s Alice-in-Wonderland terrain. Some of these unusual experiments were captured on film for use in military training videos.

One place where ARTICHOKE research took place was the Addiction Research Centre at the Public Health Service Hospital in Lexington, Kentucky—the same hospital that specialized in the treatment of hardcore heroin addicts. Lexington was part hospital and part penitentiary, which made it perfect for human experimentation. The addict/inmates of Lexington were sometimes given LSD without their consent, a practice also conducted at the federal prison in Atlanta, and at the Bordentown Reformatory in New Jersey. 

In 1953, then-CIA director Allen Dulles authorized Operation MK-ULTRA, which superseded earlier clandestine drug investigations. Under the direction of Dr. Sidney Gottlieb, a chemist, the government began slipping LSD and other psychoactive drugs to unwitting military personnel. During a work retreat in Maryland that year, technicians from both the Army and the CIA were dosed without their knowledge, and were later told that they had ingested a mind-altering drug. Dr. Frank Olson, a civilian biochemist involved in research on biological warfare, wandered away from the gathering in a confused state, and committed suicide a few days later by leaping to his death from an upper floor of the Statler Hilton in New York City. The truth about Olson’s death was kept secret from his family, and from the rest of the nation, for more than twenty years. In 1966, LSD was added to the federal schedule of controlled substances, in the same category as heroin and amphetamine. Simple possession became a felony. The Feds had turned off the spigot, and the research came to a halt. Federal drug enforcement agents began showing up at the homes and offices of well-known West Coast therapists, demanding the surrender of all stockpiles of LSD-25. The original acid elite was being hounded, harassed, and threatened in a rancid atmosphere of pharmaceutical McCarthyism. Aldous Huxley, Humphrey Osmond, even father figure Albert Hoffman, all viewed these American developments with dismay. The carefully refined parameters and preparations, the attention to set and setting, the concerns over dosage, had gone out the window, replaced by a massive, uncontrolled experiment in the streets. Small wonder, then, that the circus atmosphere of the Haight-Ashbury “Summer of Love” in 1967 seemed so badly timed. Countercultural figures were extolling the virtues of LSD for the masses—not just for research, not just for therapy, not as part of some ancient religious ritual—but also just for the freewheeling American hell of it. What could be more democratic than the act of liberating the most powerful mind-altering drug known to man?

It is at least conceivable that researchers and clinicians eventually would have backed away from LSD anyway, on the grounds that the drug’s effects were simply too weird and unpredictable to conform to the rigorous dictates of clinical studies. Nonetheless, researchers had been given a glimpse down a long, strange tunnel, before federal authorities put an end to the research.

—Excerpted from The Chemical Carousel: What Science Tells Us About Beating Addiction

Graphics Credit: http://news.sky.com

Interview with Deni Carise, Chief Clinical Officer of Phoenix House

Why addiction treatment works—if you let it.

This time around, our “Five-Question Interview” series features clinical psychologist Deni Carise, senior vice president and chief clinical officer at Phoenix House, a leading non-profit drug treatment organization with more than 100 programs in 10 states. Chances are, you may have seen or heard her already: Dr. Carise has been a guest commentator about drugs and addiction for Nightline, ABC’s Good Morning America, Fox News, and local New York media outlets. She is frequently quoted in US News and World Report and other periodicals, blogs at Huffington Post, and has also consulted for the U.N. Office on Drugs and Crime.

Dr. Carise earned her doctorate at Drexel University, and served as a post-doctoral fellow at the Center for Studies of Addiction at the University of Pennsylvania. Currently, she is also adjunct clinical professor in the University of Pennsylvania’s Department of Psychiatry. She has been involved with drug abuse treatment and research for more than 25 years, and has worked extensively in developing countries to integrate science-based drug treatments into local programs. She has worked with adults and adolescent populations including dually diagnosed clients, Native Americans, and with medical populations (including spinal cord-injured, cardiac care and trauma patients).

1. As chief clinical officer for Phoenix House Foundation, what's your job description?

Deni Carise: My main responsibility is to ensure that we provide the highest possible standard of care. This means making sure that treatment methods across our programs are consistent with the latest research, represent a variety of evidence-based practices, and are delivered with fidelity. I also collaborate on the implementation and evaluation of Phoenix House’s national and regional strategies to achieve clinical excellence. My home base is New York, but I work directly with all of our programs and regularly travel to our California, New England, Mid-Atlantic, Texas, and Florida regions. I also oversee the activities of our Family Services, Quality Assurance, Research, Workforce Development, and Training initiatives. Finally, I help Phoenix House spread awareness to the public about the need to reduce the stigma of addiction and to increase access to treatment services.

2. As a clinical psychologist, how did you become involved in drug and alcohol treatment and recovery?

Deni Carise: I actually became involved in the Substance Abuse Treatment (SAT) field prior to becoming a clinical psychologist. When I decided that I wanted to get sober, I got some help from a counselor. This counselor was so helpful to my recovery that I decided to become an SA counselor so that I could assist others on this journey. I was working as a model at that time, and there were a few aspects of that career that I didn’t like: First, it was very clear that I would become less valuable in my career as I got older; secondly, my value was exclusively based on appearance, not knowledge or skills; and finally, my work didn’t contribute to the greater good—that is, no one benefitted by my work. I wanted a new career where I would become more valuable as I got older and more experienced, and where my knowledge and skills would be of value. I also wanted to do something I felt was contributing to society. The SAT field seemed to fit all these criteria.

3. What makes it so difficult for people to accept the disease components of serious drug addiction?

Deni Carise: People have difficulty accepting the disease concept of addiction for three reasons. First, people believe addiction is self-induced; you wouldn’t have it if you didn’t use drugs, right? There is some truth to this, but of all those who try drugs, an estimated 5 to 10% (depending on the drug) will become addicted. There’s a reason why the other 90 to 95% don’t become addicted.

That brings us to reason #2: People generally don’t believe there is a genetic cause. It is now very clear that there is a genetic component to substance use disorders. For example, if a father is an insulin-dependent diabetic, the heritability estimates range from 70 to 90% likelihood that the man’s son will also be diabetic. For hypertension, the heritability estimates are from 25 to 50%, depending which study we look at. For alcohol, the estimates are 55 to 65% likelihood that a young man will be alcohol dependent if his father is. For opiate dependence, it’s 35 to 50%.

The third and probably most important reason is that people think calling addiction a disease absolves the substance abuser of responsibility for his or her actions. Nothing could be further from the truth. Those in recovery see the disease of alcoholism or addiction as a moral obligation to get well. If you know you have this disease and the only way to keep it under control is not to use alcohol or drugs, then that’s what you have to do.

4. Overall, treatment doesn't seem to be that effective. What's missing?

Deni Carise: I believe treatment is effective. We’re just expecting the wrong results. Substance abuse has the same characteristics as any chronic medical disorder. The problem is that we (society, families, even me) want addiction to respond to treatment as though it’s an acute medical problem, like a broken leg or appendicitis. If it were an acute problem, we could send our kids, loved ones, even ourselves to treatment for a set number of days (maybe 7, maybe 28) and leave the hospital or treatment facility with the condition cured—as we would after surgery for an appendicitis! I would love that.

Unfortunately, we’ve been measuring treatment success the same way we would for a surgical problem, even though substance abuse and dependence are, in fact, chronic problems. Think about this—substance abuse treatment success is often measured by symptoms, drug use, and life problems prior to treatment and again six months after treatment ends. Imagine if we measured success of diabetes treatment the same way. We would measure their blood sugar levels, weight, number of diabetic crises, and other related problems before treatment. Then we’d send them off to a treatment program where we would prescribe medications, maybe give them insulin, teach them about a good diet, discharge them (take away that treatment), and measure their blood sugar levels, weight, etc. six months after we stopped the medication. Do we really think that would work with diabetes? Then why would we think it would work with addiction?

As with all chronic disorders, there are no prolonged, symptom-free periods without continued attention and self-management of the illness. Just as some people with diabetes can manage their illness with behavioral changes such as making healthy decisions when offered cakes or cookies, or starting an exercise program, some people with substance abuse problems can control their symptoms by changing their behaviors. This means not being around others who use, making the right decisions when offered alcohol or drugs, etc. For those who can’t do this alone, there’s treatment to teach them how to manage their disease and there are medications to assist them. And I’m talking about the diabetic and the substance abuser.

So treatment can work, but, just like any chronic disease, there’s no quick fix.

5. You're committed to working with developing countries to bring scientifically valid treatment within reach of poorer populations. How is the effort going?

Deni Carise: I’ve been really lucky to be able to consult for numerous treatment systems, universities, and countries around the world—including training clinicians from Nigeria, Thailand, Egypt, Greece, Iran, Singapore, Brazil, China, Iraq, India, and other countries. It’s fascinating to see how different countries approach local substance abuse problems. Some countries have historically asserted that substance abuse is not a problem in their communities, so for them to offer treatment of any kind means they need to change their socipolitical stance. That doesn’t happen quickly. For one country, the diagnosis of AIDS among 7 substance abusers who had shared needles was the impetus to providing treatment.

Much of what I’ve done internationally involves cultural adaptations of standardized instruments or clinical tools (such as the Addiction Severity Index assessment tool) for use within various cultures. To do this, I typically meet with numerous staff who deliver direct services in the country. We go over each assessment question or worksheet item looking at what would make sense in their culture. Types of things that frequently need adapting are questions about education (not everyone has “high schools”), employment and income, demographic questions such as race categories, and all manner of expressions used to describe drugs and clinical symptoms. Then we pilot the new interview or service with some local clients and get their perspective and make a final version.

Much of this work has been funded by the United Nations Office on Drug Use and Crime, the National Institute on Drug Abuse and Office of National Drug Control Policy.

What is Brain Awareness Week?

Celebrate your sentience March 12-18.

Gather ‘round, children, and the Dana Foundation will tell you an amazing tale about… the You Man Brain…

Well, that is, the HUMAN brain—and the many ways of increasing understanding and awareness of this little three-pound marvel. Officially the brainchild of the Dana Alliance for Brain Initiatives in New York and the European Dana Alliance for the Brain, “Brain Awareness Week (BAW) is the global campaign to increase public awareness of the progress and benefits of brain research,” according to the BAW website.  

Founded in 1996, Brain Awareness Week is designed to unite partner organizations around the world “in a week-long celebration of the brain.” Partners include universities, hospitals, schools, government agencies, and service organizations. Partner organizations come up with creative and innovative community activities to educate people of all ages “about the brain and the promise of brain research.” For example, on Wednesday the Dana Alliance is sponsoring a “brain bee” at The Rockefeller University in New York City, where students from 21 area high schools will go head-to-head on their knowledge of neuroscience.

To see the full list of partnerships, from 41 countries, go HERE. For a list of events planned for the week, take a look HERE.  Events include open houses at neuroscience laboratories, special brain exhibitions at museums, displays and lectures at community centers, and workshops in the classroom.

If you’re feeling cocky, you can test your brain with several challenges at http://www.testmybrain.org/

Sadly, none of this hoopla will necessarily solve certain perennial brain conundrums, such as:

--If you can’t change your mind, how do you know you have one?

--Is that hole in a man’s penis really there to get oxygen to his brain?

--How can we believe that the brain is the most important organ, when the brain is the organ telling us that?

And finally, the one that keeps me awake at night:

-- How did the scarecrow know he didn't have a brain?

What Do Long Distance Running and Marijuana Have in Common?

Maybe it isn't endorphins after all.

[From time to time, I reprint earlier posts that have remained perennial favorites at Addiction Inbox. This one originally ran on August 4, 2010.]

What do long-distance running and marijuana smoking have in common? Quite possibly, more than you’d think. A growing body of research suggests that the runner’s high and the cannabis high are more similar than previously imagined.

The nature of the runner’s high is inconsistent and ephemeral, involving several key neurotransmitters and hormones, and therefore difficult to measure. Much of the evidence comes in the form of animal models. Endocannabinoids—the body’s internal cannabis—“seem to contribute to the motivational aspects of voluntary running in rodents.” Knockout mice lacking the cannabinioid CB1 receptor, it turns out, spend less time wheel running than normal mice. 

A Canadian neuroscientist who blogs as NeuroKuz suggests that “a reduction in CB1 levels could lead to less binding of endocannabinoids to receptors in brain circuits that drive motivation to exercise.” NeuroKuz speculates on why this might be the case. Physical activity and obtaining rewards are clearly linked. The fittest and fleetest obtain the most food. “A possible explanation for the runner’s high, or ‘second wind,’ a feeling of intense euphoria associated with going on a long run, is that our brains are stuck thinking that lots of exercise should be accompanied by a reward.”

In 2004, the British Journal of Sports Medicine ran a research review, “Endocannabinoids and exercise,” which seriously disputed the “endorphin hypothesis” assumed to be behind the runner’s high. To begin with, other studies have shown that exercise activates the endocannabinoid system.

“In recent years,” according to the authors, “several prominent endorphin researchers—for example, Dr Huda Akil and Dr. Solomon Snyder—have publicly criticised the hypothesis as being ‘overly simplistic,’ being ‘poorly supported by scientific evidence’, and a ‘myth perpetrated by pop culture.’” The primary problem is that the opioid system is responsible for respiratory depression, pinpoint pupils, and other effects distinctly unhelpful to runners.

The investigators wired up college students and put them to work in the gym, and found that “exercise of moderate intensity dramatically increased concentrations of anandamide in blood plasma.” The researchers break the runner’s high into four major components. Exercise, they say, “suppresses pain, induces sedation, reduces stress, and elevates mood.” Some of the parallels with the cannabis high are not hard to tease out: “Analgesia, sedation (post-exercise calm or glow), a reduction in anxiety, euphoria, and difficulties in estimating the passage of time.”

There are cannabinoid receptors in muscles, skin and the lungs. Intriguingly, the authors suggest that unlike “other rhythmic endurance activities such as swimming, running is a weight bearing sport in which the feet must absorb the ‘pounding of the pavement.’” Swimming, the authors speculate, “may not stimulate endocannabinoid release to as great an extent as running.” Moreover, “cannabinoids produce neither the respiratory depression, meiosis, or strong inhibition of gastrointestinal motility associated with opiates and opioids. This is because there are few CB1 receptors in the brainstem and, apparently, the large intestine.”

A big question remains: What about running and the “motor inhibition” characteristic of high-dose cannabis? (An inhibition that may make cannabis useful in the treatment of movement disorders like tremors or tics.) Running a marathon is not the first thing on the minds of most people after getting high on marijuana.  The paper maintains, however, that at low doses, “cannabinoids tend to produce hyperactivity,” at least in animal models. The CB1 knockout mice were abnormally inactive, due to the effect of cannabinoids on the basal ganglia. Practiced, automatic motor skills like running are controlled in part by the basal ganglia. The authors predict that “low level skills such as running, which are controlled to a higher degree by the basal ganglia than high level skills, such as basketball, hockey, or tennis, may more readily activate the endocannabinoid system.”

The authors offer other intriguing bits of evidence. Anandamide, one of the brain’s own cannabinoids, “acts as a vasodilator and products hypotension, and may thus facilitate blood flow during exercise.” In addition, “endocannabinoids and exogenous cannabinoids act as bronchodilators” and could conceivably facilitate breathing during steady exercise. The authors conclude: “Compared with the opioid analgesics, the analgesia produced by the endocannabinoid system is more consistent with exercise induced analgesia.”

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