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

Seeking a Patch or a Pill for Pot

Drug treatments for marijuana withdrawal.

Sometimes it’s easy to forget that marijuana is the most widely used illegal drug of all. We demonize it, yet we take it for granted. We punish citizens for its possession, but we call it a “soft” drug.

The idea of marijuana as an addictive drug--for some but by no means all users—still seems preposterous to a large number of recreational pot smokers. Yet these same people have far less trouble dealing with the existence of raging alcoholics surrounded by a majority of controlled, recreational drinkers or non-drinkers.

 For purposes of this post, we are going to stipulate that sufficient scientific evidence now exists to include marijuana in the category of addictive psychoactive drugs. Heavy, daily users of marijuana sometimes find themselves in an unexpected bind if they decide to quit cold. Perhaps as many as one or two in every ten heavy pot smokers will find themselves suffering from flu-like symptoms, loss of appetite, insomnia, vivid dreams, irritability, generalized anxiety, and other side effects that can be at least as unpleasant as quitting cold turkey after a long cigarette habit.

 Why didn’t we know this earlier? Perhaps for the same reasons that we didn’t know until the 1980s, as a general piece of knowledge, that cocaine was highly addictive. (Marijuana Anonymous didn’t start up until 1989). Doesn’t that sound absurd now, the state of our understanding of cocaine’s effects only 30 years ago? For people who suffer strong and repeatable withdrawal symptoms when they try to quit smoking weed, it is equally absurd to proclaim that what they are wrestling with does not resemble a genuine drug addiction (See the Addiction Inbox thread on marijuana withdrawal, which is now approaching 1,000 comments, and which constitutes a major database of self-reported data on marijuana withdrawal).

Having identified marijuana as classically addictive for a small slice of the user population, the focus has lately turned toward human laboratory studies, although most of the human studies thus far have been open-label trials rather than controlled double-blind studies. A group of researchers at Columbia University has been testing a variety of medications in search of a compound with demonstrated effects on marijuana abstinence and withdrawal. A study published online last year examines the effectiveness of a variety of medications on the course of marijuana craving and withdrawal in users classified as marijuana dependent. In other words, they are looking for the equivalent of a nicotine patch for marijuana.

In an article for CNS Drugs, Ryan Vandrey of Johns Hopkins University School of Medicine and Margaret Haney of the New York State Psychiatric Institute, surveyed such studies as presently exist on the subject of pharmacotherapy for cannabis dependence. There are presently no clinically validated treatments for marijuana withdrawal. And, unlike the hundreds of controlled, double blind trials of pharmaceuticals for addiction to alcohol, cigarettes, cocaine, and heroin, recent research on medications for marijuana dependence has been sparse and scattershot.

 Nonetheless, the marijuana withdrawal syndrome is now well established in the scientific literature, as well as anecdotally.  Among heavy dope smokers, the authors write, cold-turkey cessation from marijuana “produces cellular changes in the brain reward pathway (increased corticotrophin-releasing factor, decreased dopamine) that have been linked to the dysphoric effects associated with withdrawal from drugs such as alcohol, opiates, and cocaine, and are thought to contribute to relapse.”

What have they discovered so far?

One obvious starting point was dronabinol, a.k.a. Marinol, the government-approved synthetic THC often prescribed for nausea, vomiting, and appetite loss due to chemotherapy. Marinol is a direct approach to the nicotine patch strategy: A substance that stimulates cannabis receptors in a manner similar to, but by no means identical with, the high produced by natural marijuana. Perhaps a regular low dose of Marinol would keep the cannabis cravings at bay among problem users trying to quit. As it turns out, not really. Some studies showed that you could reduce a pot addict’s withdrawal symptoms somewhat in a home environment with Marinol, but the dose required to accomplish this was high enough to represent potential problems of its own.

Another obvious candidate for investigation was rimonabant, a.k.a. Accomplia—but for the opposite reason. Rimonabant, which started out life as an anti-obesity medication, blocks the cannabinoid receptor CB1, so in that sense it should function roughly like Antabuse for alcoholics. It is the “anti-weed,” but as it turned out, rimonabant’s effect on cannabis receptors didn’t do the trick, either. Rimonabant “reduced the effects of smoked cannabis in two studies,” Vandrey and Haney write, “but a reduction of subjective drug effects was not consistently observed.” Furthermore, rimonabant is under suspicion for causing “adverse psychiatric effects” and is not much in favor at present.

Next up, naltrexone—an opiod receptor antagonist, which blocks the effects of heroin and is used in alcohol and heroin detox and withdrawal. Naltrexone has been shown in some studies to “reduce the subjective effects of cannabinoids in humans,” the authors note. But no dice: “In cannabis users, pretreatment with high doses of naltrexone (50-200 mg) failed to attenuate, and in some cases enhanced, the subjective effects of dronabinol and smoked cannabis.” To make matters worse, “the effect of naltrexone can be overcome with higher doses of cannabis.”

Other possible anti-craving drugs for marijuana have not been as rigorously studied. An open-label investigation of buspirone, which works on serotonin and dopamine systems, caused a decline in self-reported cannabis use, and pot smokers showed marked decreases in craving and irritability—but, as these things often go, buspirone was not well-tolerated by the participants, with too many dropouts due to adverse side effects.

Lithium, a mood stabilizer commonly prescribed for bipolar disorder, has shown promise in several small studies. An open-label lithium trial by the National Drug and Alcohol Research Centre in New South Wales resulted in “significant reductions in symptoms of depression and anxiety and cannabis-related problems.” More studies are needed.

Fluoxetine, better known to the world as Prozac, has been anecdotally associated with reduced marijuana use in depressed alcohol-dependent patients, but has never been the subject of any large clinical studies with a population of users whose primary drug is marijuana.

And finally, there is a dark-horse candidate, a treatment drug sometimes employed to prevent relapse

 in cases of heroin addiction. Lofexidine is an alpha-2-adrenergic agonist that has been in use for years in the U.K. under the name BritLofex to treat the common symptoms of heroin withdrawal, such as cramps, chills, sweating, loss of appetite, and diarrhea. Similar but less intense withdrawal symptoms also afflict heavily addicted marijuana users. In a 2008 paper published in Psychopharmacology, “lofexidene was sedating, worsened abstinence-related anorexia, and did not robustly attenuate withdrawal, but improved sleep and decreased marijuana relapse.” Lofexidine combined with THC yielded even better results.

It appears that immediate research might be most profitably focused on lofexidine and lithium. And indeed, additional studies of the two drugs for cannabis dependency are planned by NIDA.  Also, the combination of dronabinol and lofexidine appears to be worth pursuing in future clinical investigations of anti-craving drugs for marijuana.

Vandrey, R., & Haney, M. (2009). Pharmacotherapy for Cannabis Dependence CNS Drugs, 23 (7), 543-553 DOI: 10.2165/00023210-200923070-00001

Graphics Credit: http://archives.drugabuse.gov

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. 

Feeling a Need for Weed?

U.K. book on cannabis dependency.

For James Langton, author of "No Need for Weed: Understanding and Breaking Cannabis Dependency", it was no easy task to find information and support when he sought to rid himself of a 30-year marijuana relationship. Through his own efforts, and the early help of Marijuana Anonymous, Langton became abstinent. And in an effort to help others in the same boat, he published his own account, a combination of personal memoir, anecdotes from pot smokers drawn to his own Clearhead support website, and a thoughtful assessment of the nature of both active marijuana dependency and marijuana withdrawal.

Langton has written a valuable and insightful book, dedicated, he says, to those "who fell blindly in love with the drug, in all its forms, without a second thought. But this book is also for those who, just like me, found that ending this love affair was much more difficult than they could ever have imagined...."

The delights of pot are self-evident: "It didn't feel wrong, dangerous or difficult; I just enjoyed life more when my senses were heightened and when I allowed the reality of everyday life to become a little distorted. After a couple of tokes, I seemed to feel the disparate parts of my consciousness clicking into place."

So why quit at all? "For a start," writes Langton, "I wanted to be clearheaded again; to be able to remember things; to be aware of time passing at normal speed, not stretched or shrunk. I wanted more of a social life. I wanted to be more confident and not so self-obsessed. I wanted to be in control and less lazy." Finally, he felt ready to "turn away from a pleasure that had evolved into a routine, then into a habit, and finally into full-blown dependency."

Metabolically, Langton had reached a point of addiction: "I needed to smoke just to feel normal. My tolerance for dope had reached such a point that if the THC in my system fell below a certain level I would feel a deep lack, a terrible emptiness."

The author found that one aspect made quitting "harder and more demoralizing" than necessary --"the almost universal dismissal from the medical and drug treatment professions about the reality of cannabis withdrawal.... very little specialist help is available to anybody who has lost control over their dope smoking."

Langton's explanation of what had happened to him is simple and understandable: "Our dopamine levels aren't meant to be tuned to such a high pitch on an everyday basis. Maybe a few times a month or the occasional binge, but if you're smoking relentlessly day after day, particularly strong skunk, then is it any wonder you might find it hard to take pleasure in the ordinary things of life?"

Langton also offers vivid descriptions of common withdrawal effects, including "the feeling of being overwhelmed by even the simplest interactions with other people, or becoming frustrated by what you would normally consider straightforward tasks." He also noted that "night sweats are difficult because, combined with light sleeping, they can cause discomfort to your partner as well.... The sweating can last for anything up to 21 days, but usually you are over the worst after about 10." In addition, Langton suggests that if you are experiencing an extreme loss of appetite, "be reassured that this is a very common symptom. The important thing is to make sure you are taking some nutrients onboard, otherwise you will start to feel week, light-headed and slightly sick." He warns of vivid dreams, and episodes of outsized anger. (The author's salient advice on anger: You can take it back.) As for energy levels, the whole withdrawal experience can "feel like jet lag, and the best advice is to treat it as such; in other words, try not to go to bed as soon as you come home from work..."

How long does it take? "At Clearhead we have found that it takes, on average, around four to six weeks for most people to fully adjust to not using cannabis.... others will still hit upon lingering symptoms up to two months after smoking their last joint."

Overall, a good read, full of telling anecdotes, personal honesty, and practical advice.