A Roundtable Discussion on Cannabis Use Disorder

Addressing the habit-forming aspects of marijuana.

A trio of leading marijuana scientists participated in a panel discussion moderated by Dr. Daniele Piomelli from the School of Medicine at the University of California-Irvine, and published in a recent issue of the journal Cannabis and Cannabinoid Research.

Dr. Margaret Haney is with the New York State Psychiatric Institute at Columbia University Medical Center; Dr. Alan J. Budney is affiliated with the Geisel School of Medicine at Dartmouth College; and Dr. Pier Vincenzo Piazza works at the Magendie Neurocenter in Bordeaux, France.

Excerpts from the long discussion appear below:

It seems that most specialists in the field agree that Cannabis is addictive. If you had to choose one piece of evidence, either clinical evidence or animal experiment evidence, in support of this conclusion, which one would you pick?

Dr. Margaret Haney: “One of the key features for me is demonstrating that there is a pharmacologically specific withdrawal from Cannabis use…. We can demonstrate that daily smokers go through a time-dependent and pharmacologically specific withdrawal when they abstain from Cannabis…. I think another really important feature is the clinical data showing how high relapse rates are with Cannabis. Although Cannabis may have a lower abuse liability than other drugs like cocaine or nicotine, once somebody has developed a dependence on the drug, then quitting becomes extremely difficult.

Dr. Alan J. Budney: “If I had to pick out the ‘smoking gun’ to convince the public and the scientific world that Cannabis Use Disorder (CUD) is real, then it would be the data from clinical epidemiological research…. the data on CUDs are remarkably similar to the other substance use disorders…. for a substantial number of people, Cannabis use causes similar and substantial problems that are comparable to other types of drugs that we all agree have addictive potential.”

Dr. Pier Vincenzo Piazza: “[In] Australia, Canada, the United States, and the European Union, over the last two years Cannabis represents the highest new entries for treatment in specialized centers…. Since these four countries have very different rates of referral of patients by the judicial system, these figures really mean that patients experience a discomfort high enough to spontaneously seek treatment…. In France, for example, as well as in many other European countries, referral from the judicial system is very low. Nevertheless, the demand for treatment for CUD is now the highest of all drugs, legal and illegal.”

What is curious is that we now accept the concept that Cannabis is addictive, but for many years we have been told that it was not. Why is it that, for so long, the scientific community failed to recognize the addictive properties of Cannabis?

Dr. Margaret Haney: “I have been speaking about Cannabis addiction for 20 years and was met by full-on boredom for the first 15 years because I felt that scientists, like the public at large, just viewed Cannabis as a benign compound not too different from caffeine in a way…. THC is lipophilic, and so long-lasting, withdrawal takes quite a while to manifest…. if an individual is dependent on nicotine, he or she cannot go a couple of hours without experiencing withdrawal. A heavy Cannabis user, by contrast, has to go quite a while before experiencing withdrawal, and so it was not quite as obvious to people that withdrawal existed.”

Dr. Alan J. Budney: “Moreover, many of those that have experience with using Cannabis, do not get addicted, develop problems, or experience withdrawal. Although the same is true for those who have used alcohol or even opiates, for reasons that are not completely clear, the personal experience of those who used Cannabis and did not develop problems or experience withdrawal, seems to lead to the perception that Cannabis is not a substance that others can become addicted to.”

Dr. Pier Vincenzo Piazza: “What we know now is that, since cannabidiol is an antagonist of THC, the greater the ratio between THC and cannabidiol the greater the risk for Cannabis to be addictive…. Now, we are up to a 5- to 10-fold difference in favor of THC, making Cannabis more addictive.”

How addictive is Cannabis? Is it more addictive than, say, tobacco or alcohol? Is it less addictive? Is this question even correctly asked? Is there a better way to ask it?

Dr. Alan J. Budney: [I] would like to emphasize a point so that our audience does not think we are going way overboard and engaging in reefer madness related to the severity of Cannabis addiction. All factors held constant, the pharmacology of opiates would probably produce a more severe addiction…. Access, dose, route of administration, societal acceptance, perceived risk, cost, societal consequences for use or intoxication, and multiple other factors contribute to the real-world question of how addictive a drug is compared to another.”

Dr. Margaret Haney: “My opinion is that Cannabis has a lower abuse liability than something like cocaine [but] even if Cannabis has a lower abuse liability, the sheer number of people using it will result in a large number of people with a use disorder….”

Dr. Pier Vincenzo Piazza: “If we try to express abuse liability in numbers, the abuse liability for Cannabis… is between 10% and 15%, depending on the survey you look at. However, I believe that abuse liability should also be measured by a second factor; that is, how easy it is to quit if you have developed a substance use disorder. My understanding… is that stopping Cannabis use, if you have developed CUD, is not easier than other drugs.”

The major point, all three experts agree, is that marijuana cannot be considered a completely benign drug. “Cannabis is not the worst drug,” says Dr. Haney, “but it is not a drug without consequences. Again, societal attitudes often seem to skew one way or the other; it is all good or it is all bad, when it is clearly both.”

Graphics Credit: hhttp://moodsurfing.com

The Blunt Facts About Blunts

Mixing 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 published in the journal Addiction, and authored by Arpana Agrawal and Michael T. Lynskey of Washington University School of Medicine, with 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://www.hightimes.com/

(First published at Addiction Inbox on March 22, 2012).

Hunting For the Marijuana-Dopamine Connection

Why do heavy pot smokers show a blunted reaction to stimulants?

Most drugs of abuse increase dopamine transmission in the brain, and indeed, this is thought to be the basic neural mechanism underlying the rewarding effects of addictive drugs. But in the case of marijuana, the dopamine connection is not so clear-cut. Evidence has been found both for and against the notion of increases in dopamine signaling during marijuana intoxication.

Marijuana has always been the odd duck in the pond, research-wise. Partly this is due to longstanding federal intransigence toward cannabis research, and partly it is because cannabis, chemically speaking, is damnably complicated. The question of marijuana’s effect on dopamine transmission came under strong scrutiny a few years ago, when UK researchers began beating the drums for a theory that chronic consumption of strong cannabis can not only trigger episodes of psychosis, but can be viewed as the actual cause of schizophrenia in some cases.

It sounded like a new version of the old reefer madness, but this time around, the researchers raising their eyebrows had a new fact at hand: Modern marijuana is several times stronger than marijuana in use decades ago. Selective breeding for high THC content has produced some truly formidable strains of pot, even if cooler heads have slowly prevailed on the schizophrenia issue.

One of the reports helping to bank the fires on this notion appeared recently in the Proceedings of the National Academy of Sciences (PNAS). Joanna S. Fowler of the Biosciences Department at Brookhaven National Laboratory, Director Nora Volkow of the National Institute on Drug Abuse (NIDA), and other researchers compared brain dopamine reactivity in healthy controls and heavy marijuana users, using PET scans. For measuring dopamine reactivity, the researchers chose methylphenidate, better known as Ritalin, the psychostimulant frequently prescribed for attention-deficit hyperactivity disorder (ADHD). Ritalin basically functions as a dopamine reuptake inhibitor, meaning that the use of Ritalin leads to increased concentrations of synaptic dopamine.

In the study, heavy marijuana users showed a blunted reaction to the stimulant Ritalin due to reductions in brain dopamine release, according to the research. “The potency of methylphenidate (MP) was also reported to be stronger by the controls than by the marijuana abusers." And in marijuana abusers, Ritalin caused an increase in craving for marijuana and cigarettes.

 “We found that marijuana abusers display attenuated dopamine responses to MP including reduced decreases in striatal distribution volumes,” according to the study’s conclusion. “The significantly attenuated behavioral and striatal distribution volumes response to MP in marijuana abusers compared to controls, indicates reduced brain reactivity to dopamine stimulation that in the ventral striatum might contribute to negative emotionality and drug craving.”

Down-regulation from extended abuse is another complicated aspect of this: “Although, to our knowledge, this is the first clinical report of an attenuation of the effects of MP in marijuana abusers, a preclinical study had reported that rats treated chronically with THC exhibited attenuated locomotor responses to amphetamine. Such blunted responses to MP could reflect neuroadaptations from repeated marijuana abuse, such as downregulation of DA transporters.”

 Animal studies have suggested that these dopamine alterations are reversible over time.

Another recent study came to essentially the same conclusions. Writing in Biological Psychiatry, a group of British researchers led by Michael A.P. Bloomfield and Oliver D. Howes analyzed dope smokers who experienced psychotic symptoms when they were intoxicated. They looked for evidence of a link between cannabis use and psychosis and concluded: “These findings indicate that chronic cannabis use is associated with reduced dopamine synthesis capacity and question the hypothesis that cannabis increases the risk of psychotic disorders by inducing the same dopaminergic alterations seen in schizophrenia.” And again, the higher the level of current cannabis use, the lower the level of striatal dopamine synthesis capacity.  As for mechanisms, the investigators ran up against similar causation problems: “One explanation for our findings is that chronic cannabis use is associated with dopaminergic down-regulation. This might underlie amotivation and reduced reward sensitivity in chronic cannabis users. Alternatively, preclinical evidence suggests that low dopamine neurotransmission may predispose an individual to substance use.”

The findings of diminished responses to Ritalin in heavy marijuana users may have clinical implications, suggesting that marijuana abusers with ADHD may experience reduced benefits from stimulant medications.

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

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

Marijuana Dependence and Legalization

Making best guesses about pot.

One essential question about state marijuana legalization continues to dog the debate:  Namely, as marijuana becomes gradually legal, how do we estimate how many people will become dependent? How can we estimate the number of cannabis users who will become addicted under legalization, and who otherwise would not have succumbed?

Back in 2011, neuroscientist Michael Taffe of the Scripps Research Institute in San Diego, writing on the blog TL neuro, referenced this common question, noting that “the specific estimate of dependence rate will quite likely vary depending on what is used as the population of interest… Obviously, changing the size of the underlying population is going to change the estimated rate….”

But change it how, and by how much? The truth is, we don’t know. We can’t know in advance. There are sound arguments for both positions: Legal marijuana will lead to increased rates of cannabis addiction because of lower price and greater availability. On the other hand, almost everybody likely to become addicted to marijuana has probably already been exposed to it, including teens.

What we can start attempting to find out with greater rigor, however, is this: How many chronically addicted marijuana users are out there right now?

In The Pathophysiology of Addiction  by George Koob, Denise Kandel, and Nora Volkow (2008), the base rate of cannabis dependence was estimated to be 10.3% for male users and 8.7% for female users. Their data came from the National Survey on Drug Use and Health, and the rate is similar to common estimates for prescription stimulant addiction. The dependence rate for cigarettes is at least three times as high. However, an overall dependence rate of 9.7%, when men and women smokers are combined, is the origin of the highly contested figure of 10%.

Since then, other databases have been tapped for estimates of existing cannabis dependence. In October of 2013, using the Global Burden of Disease database maintained by the World Bank, British and Australian researchers, along with collaborators at the University of Washington in the U.S., published revised estimates in the open-access journal PLOS ONE, based on numbers from 2010.  The scientists culled and pooled a series of epidemiological estimates and concluded that roughly 11 million cases of cannabis dependence existed worldwide in 1990, compared to 13 million cases in 2010. This boost can be accounted for in part by population increases.

Are these dependent users distributed evenly across the globe? They are not. The PLOS ONE paper demonstrates that marijuana use is markedly more prevalent in certain regions: “Levels of cannabis dependence were significantly higher in a number of high income countries including Australia, New Zealand, the United States, Canada, and a number of Western European countries including the United Kingdom.” High income equals high marijuana usage and dependence—“Cannabis dependence in Australasia was about 8 times higher than prevalence in Sub-Saharan Africa West.” But there may be major holes in the epidemiological database: “This is particularly the case for low income countries, where there is typically limited information on use occurring, even less on levels of use, and usually no data on prevalence of dependence.”

In conclusion, the researchers found an age and sex-standardized cannabis addiction prevalence of 0.2%. “Prevalence was not estimated to have changed significantly from 1990, although increased population size produced an increase in the number of cases of cannabis dependence over the period.”

In another 2008 study, this one published in the Journal of Clinical Psychiatry, scientists at Columbia University and the New York State Psychiatric Institute looked at a set of 2,613 frequent cannabis users, using the development of significant withdrawal symptoms as the leading indicator. About 44% of regular dope smokers experienced two or more cannabis withdrawal symptoms, while about 35% reported three or more symptoms. The most prevalent symptoms in this study were fatigue, weakness, anxiety, and depressed mood. “Over two-thirds smoked more than 1 joint/day on days they smoked during their period of heaviest use; mean joints smoked/day was 3.9. About one-fifth had primary major depression….”

Age of onset was not predictive of withdrawal symptoms in this large study. The investigators suggest that “irritability and anxiety may receive great clinical consensus as regular features of cannabis withdrawal because they are subjectively and clinically striking compared to fatigue and related symptoms.” The researchers also speculate that somatic symptoms of weakness and fatigue might be attributed to varying levels of THC, compared to the presence of other cannabinoids such as CBD. The study is further evidence supporting an “association of primary panic disorder or major depression with cannabis depression/anxiety withdrawal symptoms,” suggesting a “possible common vulnerability, meriting further investigation.”

One of the reasons this matters is because of the very tight relationship between marijuana addiction and major depressive disorder. A 2008 study of young adults in the journal Addictive Behaviors  found that participants with comorbid cannabis dependence and major depressive disorder, the most commonly dependence symptom was withdrawal, reported by more than 90% of the subjects in the study. 73% of the subjects experienced four symptoms or more. After that, the most common symptoms were irritability (an underreported but significant behavioral problem), restlessness, anxiety, and a variety of somatic symptoms, including gastrointestinal problems, loss of appetite, and sleep disturbances, including night sweats and vivid dreaming. The authors, affiliated with University of Pittsburgh School of Medicine, concur with the conclusion of earlier researchers:  “Given the weight of evidence now supporting the clinical significance of a cannabis withdrawal syndrome, the burden of proof must rest with those who would exclude the syndrome….”

Clearly, cannabis does not contribute to the world disease burden in the same way that alcohol, nicotine, and opiods do. However, it’s fair to say that for a minority of users, cannabis dependence causes disabilities and liabilities that are not always trivial.

Mark A. R. Kleiman, a Professor of Public Policy at UCLA and a consultant to the state of Washington on marijuana legalization, told PBS:

The couple of million who stay stoned all day, every day, account for the vast bulk of the total marijuana consumed, and thus the total revenues of the illicit marijuana industry. That's typical. The money in any drug, including alcohol, is in the addicts, not the casual users. There was a big fuss during the 80s about how much casual middle-class drug use there was and how respectable folks were supporting the markets. It's certainly true that most people who are illicit drug users are employed, stable respectable citizens. But it doesn't follow that if we could get the employed, stable respectable citizens to stop using illicit drugs, the problem would mostly go away.

Who Smokes Dope, And How Much?

Marijuana stats skew perceptions of use.

Most statistical surveys of marijuana focus on a single quantitative measurement: How many people are using? But there’s a problem: More marijuana use does not necessarily translate into more marijuana users. And that’s because a clear majority of the consumption, and black market dollars, come from the heaviest smokers.

Drug policy researchers at the RAND corporation decided that frequency of use and amount of consumption were valuable parameters gone missing in most policy discussions. So they put the focus not just on use, but also on “use-days,” and pulled a number of buried tidbits from a very big data pile. If you zero in on consumption, and not just consumers, they insist, you will find a wholly different set of inferences.

For example: “Although daily/near-daily users represented less than one-quarter of past-month cannabis users in 2002 and roughly one-third of past-month users in 2011, they account for the vast majority of use-days and are thus presumably responsible for the majority of consumption,” write Rachel M. Burns and her RAND colleagues in Frontiers of Psychiatry. As with alcohol, the majority of cannabis consumption can be accounted for by a minority of users. The heaviest users, the upper 20 percent, consume 88 percent of the U.S. marijuana supply, say the RAND researchers. “Furthermore, if over time there were no change in the number of cannabis users, but the ratio of light vs. heavy users switched from 80/20 to 20/80, then consumption would increase by 250% even though there was no change whatsoever in the number of users.”

The RAND group used two data sets on cannabis consumption—the National Survey on Drug Use and Health (NSDUH) in the U.S., and the EU Drugs Markets II (EUMII) in Europe. Data included figures for past-year and past-month use, past-month use days, and past-month purchases.

Other intriguing figures come to light when you study cannabis use, as opposed to cannabis users. The researchers declared that “only 14% of past-year cannabis users [primarily males] meet the criteria for cannabis abuse or dependence, but they account for 26% of past-month days of use and 37% of past-month purchases.”

Happen to smoke blunts? That turns out to be very telling, according to the RAND study. “Perhaps the most striking contrast concerns blunts. Only 27% of past-year cannabis users report using a blunt within the last month, but those individuals account for 73% of cannabis purchases.” Casual users, it seems, don’t do blunts.

Clearly, it takes a lot of casual users to smoke as much marijuana as one heavy user. But exactly how many? The RAND researchers ran the numbers and concluded that, in terms of grams consumed per month, it would take more than 40 casual smokers to equal the intake of a single heavy user. The share of the market represented by daily/near-daily users is clearly the motive force in their analysis.

The study in Frontiers in Psychiatry also found patterns of interest on the buy side. General use took an upswing beginning in 2007. While the probability of arrest per marijuana smoking episode hovers somewhere in the neighborhood of 1 in 3,000, everything changes if you are purchasing cannabis. RAND reported that young people collectively make more purchases per day of reported use than do older users. Therefore, “statistics indicating that the burden of arrest falls disproportionately on youth relative to their share of all users may not be prima facie evidence of discrimination if making more purchases per day of use increases the risk of arrests per year of use.” Once again, those aging Baby Boomer potheads get the best deal. They have more money with which to buy bigger amounts less often, thereby greatly lessening their chances of arrest and prosecution.

This also applies to minority arrests for marijuana offenses. “Non-Hispanic blacks represent 13% of past-year cannabis users vs. 23% of drug arrests reported by those users, but they report making 24% of the buys. Thus, some of their higher arrest rate may be a consequence of purchase patterns… African-Americans may not only make more buys but also make riskier buys (e.g., more likely to buy outdoors).”

The researchers were able to draw some conclusions about the growth in marijuana usage from 2002 through 2011, based on the NSDUH data. Their main conclusion, after exploring the demographics of this 10-year record of use, is that “consumption grew primarily because of an increase in the average frequency of use, not just because of an increase in the overall number of users.”  The driver of consumption turns out to be… greater consumption. And that increased consumption is coming from… older adults. Those older adults, it turns out, are smoking more weed.

The shift is dramatic: “In 2002, there were more than three times as many youth as older adults using cannabis on a daily/near-daily basis; in 2011 there were 2.5 times more older adults than youth using on a daily/near-daily basis.” The record of alcohol and cigarette use over the same period showed no such inversion of use patterns.  And the tweeners? “In 2002, 12-17-year-olds represented 13% of daily/near-daily users; in 2011, that had dwindled to 7%.” These trends are not just the obvious result of an increase in the proportion of older adults in the population at large. Increases in the proportion of older heavy cannabis users were much greater than the general population drift.

Among the questions raised by the RAND analysis:

— Are older marijuana smokers primarily recreational, or medicinal?

—Do increased use days among older, college-educated marijuana smokers indicate greater social acceptance, or something else?

—Are younger people replacing traditional cannabis use with other substances?

—Why did Hispanic use increase more over the study period than other ethnic groups?

Burns R.M., Caulkins J.P., Everingham S.S. & Kilmer B. (2013). Statistics on Cannabis Users Skew Perceptions of Cannabis Use, Frontiers in Psychiatry, 4   DOI: 10.3389/fpsyt.2013.00138

Photo Credit: http://www.sho.com/sho/weeds/home

What Mark Kleiman Wants You To Know About Drugs

The public policy guru guiding state legalization efforts.

Mark A. R. Kleiman is the Professor of Public Policy at UCLA, editor of the Journal of Drug Policy Analysis, author of many books, and generally regarded as one of the nation’s premier voices on drug policy and criminal justice issues. Mr. Kleiman provides advice to local, state, and national governments on crime control and drug policy. When the state of Washington needed an adviser on the many policy questions they left unanswered with the passage of I-502, which legalized marijuana in that state, they turned to Kleiman.

In the past two years, Kleiman has co-authored to Q and A-style books: Drugs and Drug Policy: What Everyone Needs to Know (2011) with Jonathan P. Caulkins and Angela Hawken; and Marijuana Legalization: What Everyone Needs to Know (2012) with Hawken, Caulkins, and Beau Kilmer.

Here, excerpted from the two books, is a brief sampling of Kleiman and his colleagues on a variety of drug and alcohol issues.

Is marijuana really the nation’s leading cash crop?

“Alas, the facts say otherwise. Analyses purporting to support the claim must contort the numbers, citing the retail price of marijuana but the farmgate price of other products, or pretending that all marijuana consumed in the United States is sinsemilla, or ignoring the fact that most marijuana used in the United States is imported, or simply starting with implausible estimates of U.S. production…. marijuana [is] in the top fifteen, but not the top five, cash crops, ranking somewhere between almonds and hay, and perhaps closest to potatoes and grapes.”

How much drug-related crime, violence, and corruption would marijuana legalization eliminate?

“Not much…. Eighty-nine percent of survey respondents report obtaining marijuana most recently from a friend or relative, and more than half (58 percent) say the obtained it for free. That stands in marked contrast to low-level distribution of heroin and crack which often occurs in violent, place-based markets controlled by armed gangs.”

How much would legal marijuana cost to produce?

“The punch line is that full legalization at the national level—as opposed to only legalizing possession and retail sale—could cut production costs to just 1 percent of current wholesale prices…. This would make legal marijuana far and away the cheapest intoxicant on a per-hour basis.”

How would legalization affect me if I’m a marijuana grower?

“It would almost certainly put you out of business. At first glance, legalization might seem like a great opportunity for you…. But legalization will completely upend your industry, and the skills that made you successful at cultivating illegal crops will not have much value. A few dozen professional farmers could produce enough marijuana to meet U.S. consumption at prices small-scale producers couldn’t possibly match. Hand cultivators would be relegated to niche markets for organic or specialty strains.”

Would marijuana regulations and taxes in practice approach the public health ideal?

“If there is a licit, for-profit marijuana industry, one should expect its product design, pricing, and marketing actions to be designed to promote as much frequent use and addiction as possible. Efforts to tax and regulate in ways that promote public health would have to contend with an industry mobilizing its employees, shareholders, and consumers against any effective restriction. Since the industry profits from problem users, we should expect that lobbying effort to be devoted to blocking policies that would effectively control addiction. The alcohol and tobacco industries provide good examples.”

Can we persuade children not to use drugs?

"Even the best prevention programs have only modest effects on actual behavior, and may programs have no effect at all on drug use…. Anesthesiologists know far more about drugs and drug abuse than could possibly be taught in middle-school prevention programs; nonetheless, they have high rates of substance abuse, in part because they have such easy access.”

Why is there a shortage of drug treatment?

“Some specific categories—especially those in need of residential care, and more especially mothers with children in need of residential care—face chronic shortages. But if we had enough capacity for all those who need treatment, many of those slots would be empty because not all the people who ought to fill them want treatment.”

How much money is involved?

“Most of the numbers about drug abuse and drug trafficking that officials peddle to credulous journalists are little better than fiction. Estimates of hundreds of billions of dollars per year in international drug trade—which would make it comparable to food, oil, and arms—do not have a basis in the real world. The most recent serious estimate of the total retail illicit drug market in the United States—by all accounts the country whose residents spend the most on illicit drugs—puts the figure at about $65 billion.”

When it comes to drugs, why can’t we think calmly and play nice?

“American political analysts talk about ‘wine-track (college-educated) and ‘beer track’ (working-class) voters…. So the politics of drug policy is never very far from identity politics…. The notion that illicit drug taking is largely responsible for the plight of minorities (and of poor people generally) and that income-support programs have the perverse consequence of maintaining drug habits has been a staple of a certain form of American political rhetoric at least since Ronald Reagan.”

Are we stuck with our current alcohol problem?

"By no means…. tripling the tax would raise the price of a drink by 20 percent and reduce the volume of drinking in about the same proportion. Most of the reduced drinking would come from heavy drinkers, both because they dominate the market in volume terms and because their consumption is more price-sensitive…."

Drug News in Brief

Short takes on matters various.

Taking Aim at Pot—Researchers have recently made clinical efforts to test three drugs that might help during marijuana withdrawal to keep pot abstainers on the straight and narrow. Researchers at Columbia University, led by Margaret Haney, have been testing a synthetic THC compound called nabilone. The drug is designed to address sleep and appetite problems during withdrawal.  Whether it is any better tolerated by users than Marinol, Uncle Sam’s widely unpopular version of synthetic THC, remains to be seen. This approach can be viewed rather like methadone or buprenorphine substitution therapy. Meanwhile, work goes on with lofexidine, a drug sometimes used in combination with naltrexone for opiate detoxification. A 2008 study in Psychopharmacology showed a modest improvement over placebo when lofexidine was used for marijuana abstinence, but it worked much better when combined with, yes, synthetic THC. Finally, velafaxine, better known as the antidepressant Effexor, was used in a randomized, double-blind, placebo controlled trial of marijuana-dependent outpatients recently published in Addiction. Not only did velafaxine fail to help the patients with their cannabis dependence, but in fact “may lead to an increase in cannabis use.”

Smoking is Bad to the Bone—The Journal of Adolescent Health reports that cigarette smoking dramatically impacts the rate of bone density growth in teenage girls. Young women may be smoking their way toward a future of osteoporosis, the loss of bone density that often plagues older women. “This age group is when you should gain about 50 percent of your bone accrual,” reports study author Lorah Dorn at Cincinnati Children’s Hospital Medical Center, in Science News. A 2001 study of adult smokers found that smoking increased the risk of hip fracture by 31% in women. In addition, at the recent annual meeting of the American Academy of Orthopedic Surgeons, researchers reported on a study of 6,779 patients undergoing treatment for spinal disorders with severe pain. Those who quit smoking during treatment reported greater pain improvement than patients who didn't stop smoking. 

Dr. Google Will See You Now—Researchers are starting to data-mine the Internet to identify unanticipated side effects and interactions between prescription drugs. According to an article in Science by Sean Treacy, one study in 2011 data-mined reports to the FDA from doctors, nurses, and patients, and “uncovered a hidden drug interaction: When taken together the antidepressant paroxetine and the cholesterol suppressant pravastatin can cause hyperglycemia, or high blood sugar.”  Bioinformatics researcher Nigam Shah of Stanford told the magazine that “if a lot of people are concerned about a symptom, that in itself is valuable information.”

Fetal Health—Scientists have traced out a molecular signaling pathway that appears to play a crucial role in the development of fetal alcohol spectrum disorders (FASD). According to the researchers, whose study was published in the Proceedings of the National Academy of Sciences, “ethanol may cause FASD in part by decreasing the adhesion of the developmentally critical L1 cell adhesion molecule through interactions with an alcohol binding pocket on the extracellular domain.” In English, it means that the research points to strong candidate genes, therefore identifying a specific locus of action for future drugs designed to block alcohol neurotoxicity in the womb. A group led by Michael Charness at Harvard Medical School did the work, building on previous studies that identified the alcohol sensitivity of L1 adhesion molecules. “Prenatal alcohol exposure is the leading preventable cause of birth defects and developmental disorders in the United States,” according to perennial Acting NIAAA Director Kenneth Warren, in an NIH news release.

Photo Credit:  http://jimbaker.wordpress.com/

Does Marijuana Withdrawal Matter?

What happens to some smokers when they cut out the cannabis.

People who say they are addicted to marijuana tend to exhibit a characteristic withdrawal profile. But is cannabis withdrawal, if it actually exists, significant enough to merit clinical attention? Does it lead to relapse, or continued use despite adverse circumstances? Should it be added to the list of addictive disorders in the rewrite of the Diagnostic and Statistical Manual of Mental Disorders (DSM) currently in progress?

Marijuana fits in fairly well with the existing criteria for clinical addiction—except for one common diagnostic marker. Among the identifying criteria currently used in the DSM, we find: “The presence of characteristic withdrawal symptoms or use of substance to alleviate withdrawal.” Opponents of marijuana’s inclusion as an addictive drug have long insisted that cannabis has no characteristic withdrawal symptoms, but this position has been severely eroded of late, as new research has consistently identified a withdrawal syndrome for marijuana, which includes drug cravings, despite decades of controversy over this basic medical question.

A group of researchers at the University of New South Wales, Australia, along with Dr. Alan J. Budney of the Geisel School of Medicine at Dartmouth, New Hampshire, writing in PLOS ONE, presented evidence that the characteristic withdrawal symptoms displayed by addiction pot smokers are in fact strong enough to be considered clinically significant.
(For more on the marijuana withdrawal profile, see HERE, and HERE. For a bibliography of relevant journal articles, go HERE).

But how does one go about determining if withdrawal reactions rise to the level of clinical significance? The researchers wanted to know whether functional impairment reported during abstinence was clinically significant, whether it correlated with severity of addiction, and whether it was predictive of relapse. 46 survey volunteers who were not seeking any formal treatment for marijuana addiction were recruited in Sydney, Australia. Users ranged in age from 18 to 57, with an average age of 30. After a one-week baseline phase, the participants underwent two weeks of monitored abstinence. Using a “Severity of Dependence Scale” (SDS) to measure variability in functional impairment, the researchers compared a high SDS subgroup to a low SDS subgroup in an effort to tease out whether functional impairments in high SDS participants were predictive of relapse. The researchers noted that earlier work had established that the symptoms most likely to cause impairment to normal daily functioning were: Trouble getting to sleep, angry outbursts, cravings, loss of appetite, feeling easily irritated, and nightmares or strange dreams.” The investigators broke these symptoms into two groups: “somatic” and “negative affect” variables.

The researchers then examined self-reports about the impact of cannabis withdrawal on normal daily activities.  While the common yardstick for withdrawal is typically taken to be intensity of cravings, the authors argue that this reliance on craving “may mask the extent to which symptoms led to functional impairment, as those who maintained abstinence may still have experienced clinically significant negative consequences from cannabis withdrawal (e.g. relationship or work problems resulting from the withdrawal syndrome.”)

As might have been expected, higher levels of cannabis dependence were associated with greater functional impairment. And while the average level of functional impairment caused by cannabis is “mild for most users, it appears comparable with tobacco withdrawal which is of well established clinical significance.”

And certain symptoms were, in fact, correlative: “Increased somatic withdrawal symptoms are predictive of relapse, and…. increased physical tension is a significant predictor of relapse.”

 Physical distress, a “somatic” variable, mattered more, in terms of relapse, than the amount of marijuana smoked, or any other symptom on the roster of functional impairments—including mood and other negative affect variables.

“In conclusion,” the investigators write, “cannabis withdrawal is clinically significant because it is associated with elevated functional impairment to normal daily activities, and the more severe the withdrawal is, the more severe the functional impairment is. Elevated functional impairment from a cluster of cannabis withdrawal symptoms is associated with relapse in more severely dependent users.”

Furthermore: “Targeting the withdrawal symptoms that contribute most to functional impairment during a quit attempt might be a useful treatment approach (e.g. stress management techniques to relieve physical tension and possible pharmacological interventions for alleviating the physical aspects of withdrawal such as loss of appetite and sleep dysregulation.)”

As with most studies, there are limitations. As noted, the participants were not in a formal cessation program. And while urine tests were used, there was no external corroboration of the self reports.

Allsop, D., Copeland, J., Norberg, M., Fu, S., Molnar, A., Lewis, J., & Budney, A. (2012). Quantifying the Clinical Significance of Cannabis Withdrawal PLoS ONE, 7 (9) DOI: 10.1371/journal.pone.0044864

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

A Drug For Marijuana Withdrawal?

Researchers get good results with gabapentin.

Marijuana, as researchers and pundits never tire of pointing out, is the most widely used illegal drug in the world, by a serious margin. And while the argument still rages, for some years now drug researchers have been migrating to the camp that sees marijuana as an addictive drug for a minority of people who exhibit a propensity for addiction. The scientific literature supporting the contention of marijuana as addictive for some users is robust and growing, as is the body of anecdotal evidence.  It’s also clear that in many countries, cultures, and subcultures, combining cannabis with tobacco is a common practice that increases health risks all around.

Ongoing work at the Scripps Research Institute’s Pearson Center for Alcoholism and Addiction Research in La Jolla, California, has focused in part on the lack of FDA-approved medical therapies for treating marijuana addiction. Barbara J. Mason and coworkers at Scripps have reported preliminary success in a 12-week, double-blind, placebo-controlled pilot study with 50 treatment-seeking volunteers, using the anti-seizure drug gabapentin. Gabapentin, sold as Neurontin, pops up as a possible treatment for various forms of pain and anxiety, and sharp-eyed readers will recall that gabapentin was one of the ingredients in the now-defunct addiction drug Prometa.

Marijuana addiction numbers are hard to come by, and often inflated, since many small-time pot offenders end up in mandatory treatment programs, where they tend to be classified as marijuana addicts, whether or not that is objectively the case. Nonetheless, there are plenty of people seeking treatment on their own for cannabis dependence. For people strongly addicted to pot, the problems are very real, and withdrawal and abstinence pose serious challenges. People for whom marijuana poses no addictive threat should bear this in mind, the way casual drinkers bear in mind the existence of alcoholism in others.

The study, published recently in Neuropsychopharmacology, says that “activation of brain stress circuitry caused by chronic heavy marijuana use” can lead to withdrawal symptoms that persist “for weeks or even months, as in the case of marijuana craving and sleep disturbances.” A variety of existing medications have been tested in recent years, including buspirone, an anti-anxiety medication; Serzone, an antidepressant; and Wellbutrin, an antidepressant commonly used for smoking cessation. None of these treatments has shown any effect on cannabis use or withdrawal, according to Mason.

Gabapentin, as the name suggests, was modeled after the neurotransmitter GABA, and works via a transporter protein to raise GABA levels. Effective only for partial-onset seizures, common side effects include drowsiness, dizziness, and possible weight gain. It is a popular anti-epileptic drug, because it is relatively safe, with a low side-effect profile, compared to many of the medications in its class. For the same reasons, it is a common treatment for neuropathic pain. In addition to neuralgia, it has found some use as a migraine preventative.

Gabapentin normalizes GABA activation caused by corticotrophin-releasing factor, or CRF. CRF is a major player in the brain’s stress responses. As it turns out, withdrawal from both cannabis and alcohol ramp up anxiety levels by increasing CRF release in the amygdala, animal studies have shown. “Gabapentin had a significant effect in decreasing marijuana use over the course of treatment, relative to placebo,” the authors report. In addition, gabapentin produced “significant reductions in both the acute symptoms of withdrawal as well as in the more commonly persistent symptoms involving mood, craving, and sleep.”

As a bonus, the researchers discovered that “overall improvement in performance across cognitive measures was significantly greater for gabapentin-treated subjects compared with those receiving placebo.” Gabapentin was associated with improvement in “tasks related to neurocognitive executive functioning”—things like attention, concentration, visual-motor functioning, and inhibition. Counseling alone, represented by the placebo group, “resulted in less effective treatment of cannabis use and withdrawal, and no improvement in executive function.”

As in the case of Chantix for cigarette cessation, a treatment, which now requires additional caveats about possible suicidal ideation, researchers looking for a treatment for drug withdrawal, must weigh the benefits of pharmacological treatment against the possible side effects of the treatment itself. Does gabapentin for marijuana withdrawal pass the “Do No Harm” test? According to Mason, it does. “Gabapentin was well tolerated and without significant side effects” in the admittedly small trial study. The two groups did not differ in the number of adverse medical events reported in the first two weeks, when dropout rates due to side effects are highest in these kinds of studies. The investigators were not relying solely on self-reporting, either. They used urine drug screens, and verified that only 3% of the study sample tested positive for other drugs.

In short, the authors report that gabapentin reduced cannabis use and eased withdrawal with an acceptable safety profile and no signs of dependence. Gabapentin, the authors conclude, “may offer the most promising treatment for cannabis withdrawal and dependence studied to date.” Further clinical research is needed, of course, but the positive results of this proof-of-concept study should make funding a bit easier.

Mason, B., Crean, R., Goodell, V., Light, J., Quello, S., Shadan, F., Buffkins, K., Kyle, M., Adusumalli, M., Begovic, A., & Rao, S. (2012). A Proof-of-Concept Randomized Controlled Study of Gabapentin: Effects on Cannabis Use, Withdrawal and Executive Function Deficits in Cannabis-Dependent Adults Neuropsychopharmacology DOI: 10.1038/npp.2012.14

Photo Credit: http://pep3799.hubpages.com/

Interview with Michael Farrell of Australia’s National Drug and Alcohol Research Centre.

On prisons, pot, and the DSM-V.

(The “Five-Question Interview” series.)

Our latest participant is Professor Michael Farrell, director of the National Drug and Alcohol Research Centre (NDARC) at the University of New South Wales in Sydney, Australia. Before that, he was Professor of Addiction Psychiatry at the Institute of Psychiatry at Kings College, London. He has been a member of the WHO Expert Committee on Drug and Alcohol Dependence since 1995, and chaired the Scientific Advisory Committee of the European Monitoring Centre on Drugs and Drug Abuse (EMCDDA) in 2008 for three years. The NDARC does a wide variety of research and data collection on drug abuse, including longitudinal studies of heroin dependence, studies on the prevalence of ADHD among addicts, and evaluation studies of inner city youth at risk. Professor Farrell is a recognized expert on drug abuse in Europe, and was kind enough to share some of his thoughts with Addiction Inbox.

1. Does the National Drug and Alcohol Research Centre (NDARC) of Australia have a specific research slant, or area or interest, or do you try to cover the waterfront?

Michael Farrell: The research base of NDARC is very broad. The Australian Federal Government provides a fifth of our funding under the National Drug Strategy and this includes a brief for national monitoring of drug trends among illicit drug users and improving the evidence base around effective treatment and prevention. Our projects cover the majority of illicit drugs as well as alcohol, prescription drugs and more recently tobacco, and we have a strong international presence through our collaborations with the United Nations, the World Health Organisation and the Global Burden of Disease project.

Our current research programs include prevention, treatment evaluation, policy, law enforcement, health economics and epidemiology. NDARC has two “Centres within the Centre”—NCPIC (see below) and the Drug Policy Modelling Program (DPMP). We have teams working with school-aged children, mothers and babies, and injecting drug users. So it would be fair to say that we are covering the waterfront!

2. You have been critical of proposed revisions in the Diagnostic and Statistical Manual of Mental Disorders (DSM), particularly as they relate to alcoholism. What do you think is going wrong, and what’s going right, when it comes to DSM-V changes?

Farrell: The change in overall terminology is probably the most controversial with the reintroduction of “addiction” into the terminology. Personally I prefer “dependence” and think the measurement of dependence has continued to improve over the years. It is important that we use terms that we can measure carefully and be confident that we are all talking the same language. Alcohol abuse and alcohol dependence have been combined into a single disorder of graded severity, the criterion reflecting substance-related legal problems has been removed, and a new diagnostic criterion representing craving has been included. Finally, new diagnostic thresholds for alcohol use disorder (AUD) have been proposed. It seems that there is strong support for the first three changes. However, there is little published literature regarding the impact of the revised diagnostic threshold. Using data from a survey of over 10,000 people in the Australian general population, Mewton and colleagues at NDARC (2010) demonstrated that the prevalence of alcohol use disorder defined according to the DSM-5 was 60 per cent higher than the prevalence of the same disorder according to DSM-IV. A disorder which increases so dramatically in prevalence after applying a new definition is surely problematic.

3. Increasingly, the study of addiction has moved away from traditional medicine and psychiatry, becoming a recognized area of study in molecular biology and neuroscience. How do you personally view this shift in emphasis toward hard science?

Farrell: In reality, no professional groups have been jumping at the chance to handle addiction problems. In the early phases of treatment development it was often religious groups and humanitarian social activist groups who pioneered helping responses for marginalised groups. As the size of the problem and response has grown, thankfully it has been possible to get mainstream health and social care professionals more involved. There is still a need for more involvement. Modern young doctors need addiction treatment skills if they are to be properly equipped to practice in the 21st century.

Greater involvement of the biological sciences in the study of addiction holds out the possibility that we might get some exciting breakthroughs in understanding of behaviour, prevention, and treatment.  Goodness knows we could do with some new breakthroughs or advances in treatment! A focus on biological sciences does not need to be at the expense of the other social and epidemiological approaches, and ideally, with further investment in research around drugs, we might better understand the interactions between genes and environment.

4. NDARC also houses the National Cannabis Prevention and Information Centre (NCPIC). What is the mission there, and do you see marijuana as an addictive drug?

Farrell: NDARC is privileged to have NCPIC funded by the Federal Government as a “Centre within a Centre” and to the best of my knowledge there is nowhere like it anywhere else in the world. The mission of NCPIC is to reduce the use of cannabis in Australia. Cannabis is the most commonly consumed illicit drug in the country, with one in three (33.5%, 5.8 million) Australians aged 14 years and older reporting having used it in their lifetime. Just over one in ten (10.3%, 1.9 million) had used it in the previous twelve months. The burden of disease associated with cannabis is substantial. I have no doubt that cannabis can result in dependence, and that the stronger, more potent forms of cannabis give rise to more physical and mental health problems. Cannabis dependence seems to occur at rates similar to alcohol, but the effects of cannabis dependence can be mild, and may be associated with otherwise high levels of social function. Equally, dependence at the severe end is associated with significant harms, including poor social functioning and reduced participation in the education and the workforce.

5. You have a long-standing interest in the question of substance abuse in the prison system. Why can’t prison officials eliminate the drug trade behind bars?

Farrell: The prison authorities cannot eliminate drugs from behind bars because nearly half of all prisoners have a history of serious drug involvement. It is no more likely that we will have a drug free prison than it is that we will have a drug free society. The serious gaps in response in prisons are often quite shocking. The near complete absence of methadone or buprenorphine treatment in American prisons is hard to understand, when you see what a great contribution US research and treatment with methadone and buprenorphine has had globally. Now there are over 300,000 people on methadone in China as part of HIV and AIDS prevention.  Most countries in Europe have methadone in their prisons, and many emerging countries have developed prison methadone programmes. But in the US there are only a handful of programmes. There is a need for real change in this area as it is an incredible gap that could be readily addressed.

Overall we still have a long way to go in building an evidenced-based approach to drug prevention and treatment. We have come a fair distance in the past twenty years, but the road remains long and winding.

Photo Credit:  http://ndarc.med.unsw.edu.au/ 

Marijuana, Vomiting, and Hot Baths

A case history of cannabinoid hyperemesis.

Cannabinoid hyperemesis, as it's known, is an extremely rare but terrifying disorder marked by severe episodic vomiting that can only be relieved by hot baths. (see earlier post). Sufferers are heavy, regular cannabis users, most of them. And hot baths? Where did THAT come from?

The syndrome was first brought to wider attention last year by the anonymous biomedical researcher who calls himself Drugmonkey, who documented cases of hyperemesis that had been reported in Australia and New Zealand, as well as Omaha and Boston in the U.S. "There were two striking similarities across all these cases," Drugmonkey reported. "The first is that patients had discovered on their own that taking a hot bath or shower alleviated their symptoms. So afflicted individuals were taking multiple hot showers or baths per day to obtain symptom relief. The second similarity is, as you will have guessed, they were all cannabis users."

The reports haven't stopped. This summer, an intriguing account appeared on the official blog of New York University's Division of General Internal Medicine, where med students offered a formal definition: "A clinical syndrome characterized by intractable vomiting and abdominal pain associated with the unusual learned behavior of compulsive hot water bathing, occurring in the setting of long-term heavy marijuana use."

Still skeptical? I received this heartfelt comment on my original post a few days ago:

Listen, doubters. My son has this. He has been cyclical vomiting and spending hours in boiling hot baths since last Autumn. It's getting worse and he has lost a hell of a lot of weight. He is 21 and an addicted, heavy cannabis user who started at 15. He has tried cutting down but every other joint of weed brings on the obsession. He refuses to co operate with medical staff who try to treat him.
He has been taken to numerous hospitals as an emergency for non-stop vomiting and begs medical staff to let him sit in a very hot bath. They try the best anti-vomiting drugs instead, to no effect, and then some let him go in a hot shower for an hour plus. He always ends up on a drip and as soon as he feels well enough, discharges himself, often the same day.

At the weekend he went to a sports event in the city with friends, realised on the way he was going to have an episode, so left friends and made his way into a hotel room and locked himself in. Police were called and got him out of a boiling hot bath against his will. Cue vomiting attack so bad police called an ambulance. Once again discharged himself from hospital, demanding drip be removed or he would do it himself. Has sat in bath at house he shares with girlfriend for at least 12 hours today, she tells me. She says water is so hot she has no idea how he bears it.

He says he has no pain in stomach, just a sensation that drives his head mad and he KNOWS it will not go, or the vomiting stop, until he gets in boiling hot bath and stays there. He has even done this while abroad on holiday and ended up on a drip before being flown home.

All of this is true. A mother.

I was intrigued, and discussed this briefly with the mother, who lives in the U.K. She added a number of details in an email exchange, and agreed to let me publish her comments:

“I am a mother in the UK whose son definitely has this, but is not officially diagnosed as he ‘escapes’ medical attention by discharging himself from various hospitals.

When it happens he is desperate to get in a hot bath. He lives with his girlfriend. I only realised what the hell was really going on when she insisted on telling me, and have since been regularly involved in the hospitals saga.

When I discovered the truth I put ‘cannabis’ ‘vomiting’ and ‘hot baths’ ‘showers’ in google and up came a perfect description of what my son does.

I am trying to get him to agree to go for counselling and psychiatric help as he has reached the stage where this obsessive vomiting and bathing is wrecking his life. But every time he gets a little better he believes he can ‘control it’ which is not the case at all.

Yes – we end up in the hospitals and the first young emergency doctor who has ever smoked a joint and/or thinks he knows everything, tells G “Oh no it can’t be that, cannabis stops vomiting, not starts it.” Of course, they have never heard of this condition and just think he is being irrational because of the constant need to vomit. They are sure it is food poisoning or some kind of spasm and take basic blood tests.

They find nothing, insist on giving him the best anti-sickness drugs usually for cancer patients and so on…, saying “this will definitely stop it” and still he vomits. He is not in pain, just rapidly dehydrating and panicking and complaining of a weird sensation in his stomach. He tells them “I know it’s in my head doing this” and desperately demands to get in a bath. Even when he has arrived at hospital because police found him in a boiling hot bath, this makes no sense to the medics who only give in when none of their drugs work. He then immediately stops vomiting but is petrified of getting out of the bath. Eventually, when he says it is under control, he agrees to get out, and is put on a drip. Approx an hour later, while the doctors are planning follow-up procedures like scans and more complex blood tests etc, he starts an argument with a nurse, insists the drip is removed and phones a friend to collect him, avoiding seeking a lift from me if he can. The over-pressed doctors here (the British system is like a cattle market) are left mystified and move onto the next emergency in their pile up of admissions. And so it goes on, and will do, until G accepts even the odd joint can set him off.”
----

Researchers speculate that it has something to do with CB-1 cannabinoid receptors in the intestinal nerve plexus--but nobody really knows for sure. Low doses of THC might be anti-emetic, whereas in certain people, the high concentrations produced by long-term use could have the opposite effect.

Detoxifying with Marijuana Anonymous

                            

What MA has to say.

Marijuana Anonymous was formed in 1989 as a program for those having difficulty remaining abstinent from marijuana. It is based on the 12-Step approach formulated by Alcoholics Anonymous. The group was founded in California as an amalgamation of existing groups, such as Marijuana Smokers Anonymous in southern California and Marijuana Addicts Anonymous in San Francisco. (In 1978, Pot Smokers Anonymous was founded in New York by David and Pearl Izenzon.)

But what, exactly, does Marijuana Anonymous say about marijuana? What does the organization actually suggest, in addition to the 12 Steps, when it comes to abstaining from cannabis?

The following information was excerpted from the official home page of Marijuana Anonymous and from pamphlets made available by the group.

Can there be physical effects from quitting marijuana?

In spite of numerous years of being told that there are no physiological effects from marijuana addiction, many of our recovering members have had definite withdrawal symptoms. Whether the causes are physical or psychological, the results are physical. Others have just had emotional and mental changes as they stop using their drug of choice. There is no way of telling before quitting who will be physically uncomfortable and who will not. Most members have only minor physical discomfort if any at all. This pamphlet is for those who are having trouble and wonder what's happening to them.

What are some of the more common symptoms?

By far the most common symptom of withdrawal is insomnia. This can last from a few nights of practically no sleep at all, up to a few months of occasional sleeplessness. The next most common symptom is depression (that is, if you're not euphoric), and next are nightmares and vivid dreams. Marijuana use tends to dampen the dreaming mechanism, so that when you do get clean the dreams come back with a crash. They can be vivid color, highly emotional dreams or nightmares, even waking up then coming back to the same dream. The very vivid, every-night dreams usually don't start for about a week or so.

The fourth most common symptom is anger. This can range from a slow burning rage to constant irritability to sudden bursts of anger when least expected: anger at the world, anger at loved ones, anger at oneself, anger at being an addict and having to get clean. Emotional jags are very common, with emotions bouncing back and forth between depression, anger, and euphoria. Occasionally experienced is a feeling of fear or anxiety, a loss of the sense of humor, decreased sex drive, or increased sex drive. Most all of these symptoms fade to normal emotions by three months. Loss of concentration for the first week or month is also very common and this sometimes affects the ability to learn for a very short while.

What about physical symptoms?

The most common physical symptom is headaches. For those who have them, they can last for a few weeks up to a couple of months, with the first few days being very intense. The next most common physical symptom is night sweats, sometimes to the point of having to change night clothes. They can last from a few nights to a month or so.

One third of the addicts who responded to a questionnaire on detoxing said they had eating problems for the first few days and some for up to six weeks. Their main symptoms were loss of appetite, sometimes enough to lose weight temporarily, digestion problems or cramps after eating, and nausea, occasionally enough to vomit (only for a day or two). Most of the eating problems were totally gone before the end of a month.

The next most common physical symptoms experienced were tremors or shaking and dizziness. Less frequently experienced were kidney pains, impotency, hormone changes or imbalances, low immunity or chronic fatigue, and some minor eye problems that resolved at around two months. 

For more information, contact:

 Marijuana Anonymous World Services

P.O. Box 2912

Van Nuys, CA 91404

USA

Toll Free 1-800-766-6779

office@marijuana-anonymous.org

graphic: http://www.7h1s.com/ ©2008 - Marijuana Anonymous World Services - All Rights Reserved.