Q & A with Nora Volkow

NIDA director discusses cannabis, addiction vaccines, and gambling.

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

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

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

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

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

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

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

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

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

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

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

Marijuana Withdrawal: A Survey of Symptoms (Part 2)

By Dirk Hanson

[Originally published in The Praeger International Collection on Addictions. Ed. by Angela Browne-Miller. Westport, Connecticut: Praeger, 2009. Vol. 2 Ch. 7 pp.111-124.]


Results

All of the following comments can be found at the Addiction Inbox post on Marijuana Withdrawal. The unnumbered messages on the Web site are dated, and appear in chronological order.

Cave. (2008, February 8):

“Well I just stopped smoking pot after 4 years of everyday use, 5 days ago. I am feeling the withdrawal symptoms ridiculously hard. No appetite, slight nausea, extreme insomnia.”

Anonymous. (2008, February 26):

“My boyfriend (of 6 years) has been a smoker for approximately 16 years. He has tried to give up a few times seriously before but has never quite gotten there yet. His behavior is almost unbearable when he does. It really takes a toll on our relationship. I never realized that it could be so bad and that his actions are so exaggerated by withdrawal.”

Anonymous. (2008, February 26):

“I’m a 30-year-old man and have been a heavy cannabis user (3 to 4 joints per day, every day) since I was 19. . . . I’ve been through intense anxiety, depression, restlessness, lack of appetite. I can’t sleep for more than a few hours at a time and when I do, I sweat buckets. I have a terrible appetite, I’m cold all the time, like I can’t regulate my temperature.”

Anonymous. (2008, February 27):

“I thought I was going crazy because all other sites told me that there were no withdrawal symptoms from pot, I can’t think or eat and when I do finally get something down my gullet I get the runs straight after. . . . I feel like I have been hit by a truck and it has only been a week since I gave up.”

Anonymous. (2008, March 1):

“I am 31 and a heavy smoker of 10 years. . . . What is really troubling me, however, is the excessive dreaming. . . . The dreams are vivid and strong, enough to wake me up sometimes.”

Anonymous. (2008, March 3):

“This idea of ‘intense dreaming’ is very real and for the first 5 or 6 days after quitting I experienced life-like dreams/nightmares (99% nightmares), which would wake me from my sleep. . . . This idea of breaking out in cold sweat is also very real and quite scary when [it] occurs as [it] got me worried there was something else wrong with me.”

Scott. (2008, March 3):

“I was blown away when I saw ‘excessive sweating’ as I have been experiencing that for a few days. . . . If I could cut back drastically, that would be the ideal situation. But I know from experience that I can’t just smoke pot ‘a little bit.’ If I’m going to reduce, it’s going to have to be all the way to zero.”

Anonymous. (2008, March 7):

“I’m on day seven of abstinence and boy, do I feel lousy. Night sweats, anxiety, extreme insomnia, and loads of irritability/anger problems. . . . It’s a bit like when you have a bad flu. You plain feel rotten. Anything stress-related is magnified ten-fold.”

Bob. (2008, March 7):

“I’m 38 years old and have been using weed now daily for almost 21 years. . . . I’ve been ‘clean’ now for 4 days and so far it has obviously been difficult, but already I’m showing signs of improvement, the first two days I had no sleep at all. . . . My withdrawal symptoms: Loss of appetite, sweating, irritability, sudden crying fits.”

Anonymous. (2008, March 8):

“I am a 25-year-old female and I have been smoking pot since I was 13. I have NEVER stopped even a day that I can remember. Not unless I couldn’t get it. I have recently started to realize that it is a drug addiction. I was always on the ‘it’s not addictive’ side. I get very anxious if I think I’m not going to have any. . . . It is out of my control I think, and now I’m starting to not feel high. I REALLY wanna stop, but am so scared of the symptoms. I think I need help.”

Anonymous. (2008, March 18):

“Having read all of these comments and questions I no longer feel so abnormal. I have been experiencing most of these symptoms including vivid dreaming. . . . I have been a smoker since I was 15, every day smoking about 2–3 joints.”

Anonymous. (2008, March 24):

“I am a 25-year-old female. I started smoking at 18. . . . I quit a few weeks ago. . . . I can’t focus on anything. I can’t make myself do anything. . . . I snap at everyone, including my boyfriend who has been complaining about my excessive sweating. I didn’t even think of the sweating as a symptom until I read the other posts here.”

Anonymous. (2008, April 2):

“I just wanted to say I’m glad I found this site because as many people have noted the common wisdom is that there are few, if any, symptoms of withdrawal. . . . I’ve noticed the irritability and mood swings, which I expected, but didn’t make the connection between the vivid and frequent dreams and waking at night until I read all the other comments.”

Anonymous. (2008, April 8):

“I finally feel sane again after reading these postings. I am a 48-year-old male who has been smoking weed since 1975. Anywhere from 2–6 joints per day of good quality pot for the last four years. Decided to quit about a week ago and my life has been a living hell since. . . . Haven’t eaten a full meal in a week, very tired and depressed, stomach in knots.”

Anonymous. (2008, April 25):

“I quit weed 46 days ago. . . . pretty similar symptoms as everyone else and the most severe anxiety and depression I have ever known. . . . I can’t concentrate or focus, I can’t seem to forget about what has happened even though I want to, it feels as though my brain keeps reminding me about the ‘situation’ or some general anxious or negative thought just pops into my consciousness . . . like it’s never going to end, like my thoughts are caught in a vicious circle.”

Richard. (2008, May 3):

“It’s not suicidal ideation but it’s the feeling that life will just never ‘be right’. . . . when you suffer from symptoms that you’ve been told don’t exist, you are left looking for the wrong cause. So, if you’re told that marijuana withdrawal does not increase anxiety, anger, or ‘hopelessness,’ you want to look for a cause of those things. . . . I went through withdrawal periods where I was inappropriately angry at the wrong thing, thinking that specific PEOPLE were upsetting me when they were not.”

Discussion

The U.S. government’s essentially unchanged opposition to marijuana research has meant that, until quite recently, precious few dollars were available for research. This official recalcitrance is one of the reasons for the belated recognition and characterization of marijuana’s distinct withdrawal syndrome. According to research undertaken as part of the Collaborative Study of the Genetics of Alcoholism, 16 percent of people with a lifetime history of regular marijuana use reported a history of cannabis withdrawal symptoms (Schuckit et al., 1999, p.41). In earlier research, Mason discovered that those seeking treatment for cannabis addiction tended to cluster in two age groups—college age and mid-50s (Somers, 2008).

Budney et al. (2004, p. 1973) write:

Regarding cross-study reliability, the most consistently reported symptoms are anxiety, decreased appetite/weight loss, irritability, restlessness, sleep problems, and strange dreams. These symptoms were associated with abstinence in at least 70% of the studies in which they were measured. Other clinically important symptoms such as anger/aggression, physical discomfort (usually stomach related), depressed mood, increased craving for marijuana, and increased sweating and shakiness occurred less consistently.

Today, scientists have a much better picture of the tasks performed by anandamide, the body’s own form of THC. Among the endogenous tasks performed by anandamide are pain control, memory blocking, appetite enhancement, the suckling reflex, lowering of blood pressure during shock, and the regulation of certain immune responses. This knowledge helps shed light on the wide range of THC withdrawal symptoms, particularly anxiety, chills, sweats, flu-like physical symptoms, and decreased appetite.

Furthermore, we can look to indications for which marijuana is already being prescribed—anxiety relief, appetite enhancement (compounds similar to anandamide have been discovered in dark chocolate), suppression of nausea, relief from the symptoms of glaucoma, and amelioration of certain kinds of pain—for more insight into the common hallmarks of cannabis withdrawal.

What treatment measures can help ameliorate marijuana withdrawal and craving in heavy users who wish to quit? The immediate threat to any decision in favor of abstinence is what might fairly be called the “hair of the dog” effect. Note the findings of a 2004 paper in Neuropsychopharmacology: “Oral THC administered during marijuana abstinence decreased ratings of ‘anxious,’ ‘miserable,’ ‘trouble sleeping,’ ‘chills,’ and marijuana craving, and reversed large decreases in food intake as compared to placebo, while producing no intoxication” (Haney et al., p. 158).

Moreover, “Overall withdrawal severity associated with cannabis alone and tobacco alone was of a similar magnitude. . . . cannabis withdrawal is clinically important and warrants detailed description in the DSM–V and ICD–11” (Vandrey, Budney, Hughes, & Liguori, 2008, p. 48). It is possible that many more people are trying—and failing—to quit marijuana than researchers have previously suspected. Daily use of marijuana may be driven in part by the desire to avoid or eliminate abstinence symptoms (Haney, Ward, Comer, Foltin, & Fischman, 1999, p. 395).

To date, there is no effective anticraving medication approved for use against marijuana withdrawal syndrome. More than a decade ago, Ingrid Wickelgren wrote in Science: “For instance, chemicals that block the effects of CRF or even relaxation exercises might ameliorate the miserable moods experienced by people in THC withdrawal. In addition, opiate antagonists like naloxone may, by dampening dopamine release, block the reinforcing properties of marijuana in people” (1997, p. 1967). Since stimulation of THC receptors has homologous effects on the endogenous opioid system, various investigators have speculated that naltrexone, the drug used as an adjunct of heroin withdrawal therapy, may find use against symptoms of marijuana withdrawal in people prone to marijuana dependence (Tanda et al., 1997, p. 2049). Further research is needed on the reciprocal relationship between THC and opioid receptor systems.

Serzone (nefazodone), an antidepressant, has been used to decrease some symptoms of marijuana withdrawal in human subjects who regularly smoked six joints per day (Haney et al., 2003, p. 157). Anxiety and muscular discomfort were reduced, but Serzone had no effect on other symptoms, such as irritability and sleep problems.

Preliminary studies have found that lithium, used to treat bipolar disorder, curbed marijuana withdrawal symptoms in an animal study (Cui, Gu, Hannesson, Yu, & Zhang, 2001, p. 9867). Another drug for mania and epilepsy—Depakote—did not aid significantly in marijuana withdrawal (Haney et al., 2004, p.158).

Since difficulty sleeping is one common symptom of withdrawal, common prescription medications might be indicated for short-term use in the case of severe marijuana withdrawal. Some researchers have reported that even brief interventions, in the form of support group sessions, can be useful for dependent pot smokers (Copeland, Swift, & Rees, 2001, p. 45).

It is also plausible to suggest that the use of marijuana by abstinent substance abusers may heighten the risk of relapse. In a study of 250 patients at a psychiatric/substance abuse hospital in New York, “Postdischarge cannabis use substantially and significantly increased the hazard of first use of any substance and strongly reduced the likelihood of stable remission from use of any substance” (Aharonovich et al., 2005, p. 1507). However, the researchers found that cannabis posed a greater risk to cocaine and alcohol abusers. For heroin, “cannabis use after inpatient treatment did not significantly affect remission and relapse.”

It is surprising to note the relative paucity of previous clinical data the researchers had to work with in the case of alcohol and marijuana. “The gap in the literature concerning the relationship of cannabis use to the outcome of alcohol dependence was surprising,” according to Aharonovich and colleagues. “We were unable to find a single study that examined the effects of cannabis use on post-treatment outcome for alcohol dependence, despite the fact that the majority of patients now in treatment for alcoholism dependence also abuse other drugs. Clearly additional studies of this issue are warranted” (2005, p. 1512).

Addiction researcher Barbara Mason of the Scripps Research Institute of La Jolla, California, is overseeing a four-year study of the neurobiology of marijuana dependence under a grant from NIDA. The comprehensive project will involve both animal and human research, and will make use of state-of-the-art functional brain imaging. The federal grant will also be used as seed money for the new Translational Center on the Clinical Neurobiology of Cannabis Addiction at the Scripps Institute (“Scripps Given,” 2008).

Above all, it is time to move beyond the common mistake of assuming that if marijuana causes withdrawal in some people, then it must cause withdrawal in everybody. And if it doesn’t, it cannot be very addictive. This thinking has been overtaken by the growing understanding that a minority of people suffer a chemical propensity for marijuana addiction that puts them at high risk, compared to casual, recreational drug users. The fact that most people do not become addicted to pot and do not suffer from withdrawal is no more revealing than the fact that a majority of drinkers do not become alcoholics.

The idea of marijuana addiction and withdrawal remains controversial in both private and professional circles. For an unlucky few, a well-identified set of symptoms characterizes abstinence from heavy, daily use of pot. In this, marijuana addiction and withdrawal does not differ greatly from alcoholism—the vast majority of recreational users and drinkers will never experience it.

For those that do, however, the withdrawal symptoms of marijuana abstinence can severely impact their quality of life.

Note: Sources and references can be found at the end of Part 1 below.

[Guest Post] Conspiracy Theories on the Legalization of Marijuana

A humorous look at the pot wars.

From "WebPreneur" Sarah Scrafford comes this list of reasons not to legalize pot. As Scrafford writes, "this isn’t intended as a serious policy article (so no hate mail please!). Rather, its intended to be a chance for everyone to take a step back and laugh at some of the truly nuttiest conspiracy theories put forth from both sides of the aisle.... It is my hope that this regaining of perspective will allow people on both sides of the debate to recognize the extremes often taken and find a middle ground that in the end will serve all parties better."

The complete post can be found at Web Designs School Guide:

-- The legalization of Mary Jane will turn America’s youth into useless consumer hippies: Forget for a moment that the 2006 Monitoring the Future survey found that about two out of five seniors in high school have tried marijuana and still managed to get into Harvard and Rice. These suburbia dwellers want their three children protected from the other two.

--Legalization is just another way to quail the masses: Like the LSD and AIDS conspiracies of yesteryear, card carrying members of this covert plot think that legalizing Mary Jane would solely benefit the government. With everyone listening to reggae, there would be no time to exercise the first amendment.

--Legalization will help the terrorists win: If cannabis were made legal, the terror alert in America would rise to code ‘impending doom green’ according to these theorists. Islamic extremists have been pushing Mary Jane on otherwise responsible citizens in an effort to fund terrorist plots to take over free society. Keep in mind that these extremists have a diverse portfolio, and are also using oil, the media, and Google to supplement their incomes.

The legalization movement is an elaborate plot by pharmaceutical companies to get people addicted to drugs: The overall substance is classified by the government as a gateway drug, and may encourage people to use drugs to cure what ails them. Big companies like Pfizer and Merck & Co could benefit greatly from a society trained to use drugs to feel better.

Marijuana causes schizophrenia, and if legalized will render the masses mentally unstable: Hefty pdf documents coming from researchers in England and Australia have initially found that there might be a slight correlation between the use of marijuana and hearing voices. Experts cite that childhood use can be traced to as much as 14 per cent of psychotic episodes later in life, and suggests the legalization of marijuana would severely affect the health of generations to come. In the same articles though, stress is equally seen as a cause of schizophrenia. Commentators have largely written off these findings as anything from shoddy research to funding holes for lobbyist organizations.

Society as we know it will collapse, and anarchistic potheads will rule the world: The logic here is that once marijuana is legalized, it is only a matter of time before everything else becomes legal. Soon people will be knee deep in a plethora of mind-altering substances, and society will suffer. With everyone on an assumed perpetual high, things like traffic flow and social moirés will cease to have meaning. This classic slippery slope argument can be applied to anything, all with the eventual downfall of human society. Picture the ending scene from Planet of the Apes.

Photo Credit: blameitonthevoices.blogspot.com

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.

Annals of Addiction: Grace Slick

From The Harder They Fall

"There's a whole bunch of alcoholics on both sides of my family, but they function in the sense that everybody kept their jobs. There were no divorces, except for my grandmother, but she's not an alcoholic. She was just a wild child like I was. Our alcoholics all kept their jobs and stayed married....

"The Airplane became famous as the original psychedelic band, but personally, I was more of a drinker. Anything that was around and easy I took--marijuana was very easy to score, but alcohol was my drug of choice. That's the genetic deal going on, where I'm an addict in the sense that anything I like I'm all over. Like flies on shit! And sometimes that works out fine. Right now I'm a painter. That's how I make my living and pay the mortgage....

"In 1970, when I became pregnant with China, I wasn't conscious of addiction. My life was all just sex, drugs and rock and roll. But I'm not a moron, so I knew that what you put into your face goes into your body, and part of your body is what's living in there--the child....

"Life is now fine. My daughter is sober. China came in a couple of weeks after me. Into the same rehab. My sponsor was amused. She had never seen a mother-daughter combination in the same rehab....

"I always felt very close to the story of Alice in Wonderland for a real good reason. If you remember what happened to her, she came from a very straight-laced Episcopalian Republican background, and at some point between twelve and twenty-four--mine at about eighteen or so--you go down the rabbit hole."

Excerpted from:
The Harder They Fall, by Gary Stromberg and Jane Merrill. Center City, MN: Hazelden.

Photo Credit: Donna E. Natale Planas/Miami Herald

U.K. Marijuana Panic Continues

British Prime Minister plans to stiffen pot penalties.

The national hysteria over "skunk" marijuana shows no signs of abating in Great Britain, as Prime Minister Gordon Brown is poised to overrule his advisors and reclassify cannabis as a more dangerous drug. Lost in the debate is any semblance of reasonable discussion about scientific research on marijuana.

British health authorities continue to find the basics of cannabis to be an inscrutable mystery. Some months ago, they declared that "skunk" cannabis was linked to the onset of schizophrenia. Since no one knows what, exactly, causes schizophrenia, and recent findings continue to point toward genetic causes, this was a doubly astonishing claim.

Now, continuing in the same vein of misinformation, The University College of London reports that different strains of marijuana cause different types of psychological maladies. Recently, Prime Minister Brown "publically described new strains of cannabis as 'lethal,' as if they could trigger a fatal overdose," according to an editorial in the Guardian. The Guardian went on to note that "Whitehall's own panel of experts has concluded that increased marijuana use has not been matched by a corresponding rise in mental illness."

The move to shift marijuana to Class B status from its current Class C designation has been fueled by these dubious reports. As long as British politicians continue to believe that something called "skunk" is a new and lethal derivative of marijuana, and that it causes psychosis, schizophrenia and suicide, no substantive debate on cannabis regulation can possibly take place. Colin Blakemore, a prominent professor of neuroscience at the Universities of Oxford and Warwick, tackled the issue in an article for the Guardian:

And what of the alarming stories of horrifying powerful "skunk"? Some newspapers have told us that the level of THC, the active ingredient, in street cannabis today is 20 or 30 times higher than 10 years ago. That would be rather surprising, given that THC content was 7 per cent on average in 1995. In reality, two studies, due to be published later this year, concluded that the average THC content has doubled.

Professor David Clark, a British psychologist who maintains a substance abuse information service called Wired In, writes on his blog: " I have to confess that I really cannot see what reclassifying the drug will do, other than criminalise and alienate more of our young people. It won't reduce harms that the drug can cause to some people. In saying this, I am not arguing that cannabis is safe - but nor are alcohol, tobacco and a wide range of prescription drugs which are all legal. "

addiction drugs

Marijuana Withdrawal Syndrome: A Bibliography

Selected science references.

The idea of marijuana addiction and withdrawal remains controversial in both private and scientific circles. For an unlucky few, a well-identified set of symptoms characterizes abstinence from heavy, daily use of pot. In this respect, marijuana addiction and withdrawal does not differ greatly from alcoholism--the vast majority of recreational users and drinkers will never experience it.

For those that do, however, the withdrawal symptoms of marijuana abstinence can severely impact their quality of life. Since discussions of this topic frequently veer off into sociopolitical arguments, leaving the science behind, I offer below a sampling of the growing medical and psychiatric literature on this aspect of drug use and abuse.

For additional comments and discussions about symptoms, see Marijuana Withdrawal.

References

Aharonovich, E., Liu, X., Samet, S., Nunes, E., Waxman, R., & Hasin, D. (2005). Postdischarge Cannabis Use and Its Relationship to Cocaine, Alcohol, and Heroin Use: A Prospective Study. American Journal of Psychiatry, 162(8), 1507-1514.

Budney, Alan J., Hughes, J.R., Moore, B.A., & Vandrey, R. (2004, November). Review of the Validity and Significance of Cannabis Withdrawal Syndrome. American Journal of Psychiatry, 161, 1967-1977.

Budney, A.J., Moore, B.A., Vandrey, R., Hughes, J.R. (2003). The time course and significance of cannabis withdrawal. Journal of Abnormal Psychology, 112, 393-402.

Budney, A.J., Hughes, J.R., Moore, B.A., & Novy, P.L. (2001). Marijuana Abstinence Effects in Marijuana Smokers Maintained in Their Home Environment. Archives of General Psychiatry, 58(10), 917-924.

Budney A. J., Novy P. L., & Hughes, J. R. (1999, September 1). Marijuana withdrawal among adults seeking treatment for marijuana dependence. Addiction, 94, 1311-1322.

Copeland, J., Swift, W., & Rees, V. (2001 January). Clinical profile of participants in a brief intervention program for cannabis use disorder. Journal of Substance Abuse Treatment, 20(1), 45-52.

Cui, S.S., Gu, G.B., Hannesson, D.K., Yu, P.H., & Zhang, X. (2001, December 15). Prevention of cannabinoid withdrawal syndrome by lithium: involvement of oxytocinergic neuronal activation. Journal of Neuroscience, 21(24), 9867-9876.

de Fonseca, F.R., Rocío, M., Carrera, A., Navarro, M., Koob, G.F., & Weiss, F. (1997, June 27). Activation of Corticotropin-Releasing Factor in the Limbic System During Cannabinoid Withdrawal. Science, 276, 2050 - 2054.

Department of Health and Human Services, Substance Abuse and Mental Health Services Administration. (2006). Results from the 2006 National Survey on Drug Use and Health: National Findings. Rockville, MD: Office of Applied Studies. Retrieved March 12, 2008, from http://www.oas.samhsa.gov/NSDUH/2k6NSDUH/2k6results.cfm#Ch2

Fackelmann, K.A. (1993, February 6). Marijuana and the brain: scientists discover the brain's own THC-delta-9-tetrahydrocannabinol. Science News.

Hall, W., Solowij, N., & Lemon, J. (1999). The health and psychological consequences of cannabis use. (National Task Force on Cannabis Australia, Monograph Series No. 25). Sydney, NSW: University of New South Wales, National Drug and Alcohol Research Centre.
Haney, M., Hart, C.L., Vosburg, S.K., Nasser, J., Bennetti, A., Zubaran, C., et. al. (2004). Marijuana Withdrawal in Humans: Effects of Oral THC or Divalproex. Neuropsychopharmacology, 29, 158–170.

Haney, M., Hart, Carl L., Ward, Amie S., & Foltin, R. W. (2003, January). Nefazodone decreases anxiety during marijuana withdrawal in humans. Psychopharmacology, 165(2), 157-165.

Haney, M., Ward, A.S., Comer, S.D., Foltin, R.W., & Fischman, M.W. (1999, February). Abstinence symptoms following smoked marijuana in humans. Psychopharmacology, 141(4), 395-404.

Jones, R.T., Benowitz, N.L., & Herning, R.I. (1981, August-September). Clinical relevance of cannabis tolerance and dependence. Journal of Clinical Pharmacology, 8-9 Suppl., 143-152.

Joy, J.E., Watson, S.J.,Benson, J.A. (1999). Marijuana and Medicine: Assessing the Science Base. p.92. Institute of Medicine, Division of Neuroscience and Behavioral Health. Washington. D.C.: National Academy Press. Retrieved March 5, 2008, from

Kouri, E.M., & Pope, H.G., Jr. (2000, November). Abstinence symptoms during withdrawal from chronic marijuana use. Experimental and Clinical Psychopharmacology, 8(4), 483-492.

Kouri, E.M. (2002, February 1). Does Marijuana Withdrawal Syndrome Exist? Psychiatric Times, 19(2).

Lichtman, A.H., and Martin, B.R. (2002). Marijuana Withdrawal Syndrome in the Animal Model. Journal of Clinical Pharmacology, 42, 20s-27s.

National Institute on Drug Abuse. (1999, April 20). Chronic Marijuana Users Become Aggressive During Withdrawal. NIDA News Release. Rockville, MD: National Institutes of Health, National Institute on Drug Abuse.

Schuckit, M.A., Daeppen, J-B., Danko, G.P., Tripp, M.L., Li, T-K., Hesselbrock, V.M., et. al. (1999). Clinical implications for four drugs of the DSM-IV distinction between substance dependence with and without a physiological component. American Journal of Psychiatry, 156, 41-49.

Scripps given $4M grant to study effects of marijuana. (2008, March 15). North County Times.

Somers, T. (2008, March 14). Study aims to clear haze surrounding pot addiction. San Diego Union-Tribune.

Tanda, G., Pontieri, F.E., & Di Chiara, G. (1997, June 27). Cannabinoid and Heroin Activation of Mesolimbic Dopamine Transmission by a Common µ1 Opioid Receptor Mechanism. Science, 276, 2048 - 2050.

Vandrey, R.G., Budney, A.J., Hughes, J.R., & A. Liguori. (2008, January 1). A within-subject comparison of withdrawal symptoms during abstinence from cannabis, tobacco, and both substances. Drug and Alcohol Dependence, 92, 48-54.

Wickelgren, I. (1997, June 27). Marijuana: Harder Than Thought? Science, 76, 1967-1968.

Wilson, R.I. & Nicoll, R.A. (2001, March 29). Endogenous cannabinoids mediate retrograde signalling at hippocampal synapses. Nature, 410, 588-592.

Zickler, P. (2002, October 17). Study Demonstrates That Marijuana Smokers Experience Significant Withdrawal. NIDA Notes, 17(3). Bethesda, MD: National Institutes of Health, National Institute on Drug Abuse.

Drug Use State-By-State

Vermont leads nation in marijuana use

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

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

Marijuana Fact and Fiction

Why cannabis research is a good idea.

There is little doubt among responsible researchers that marijuana--although it is addictive for some people--is sometimes a clinically useful drug. However, there is little incentive for commercial pharmaceutical houses to pursue research on the cannabis plant itself, since they cannot patent it.

The use of marijuana in the treatment of glaucoma is well established. As for the relief of nausea caused by chemotherapy, the precise “antiemetic” mechanism has not yet been identified, but several studies show that marijuana works at least as well as the popular remedy Compazine for controlling nausea. Cancer patients have used marijuana successfully to increase appetite and combat severe weight loss.

Yet another intriguing possibility centers on Huntington’s chorea, the single-gene disease researchers spent years chasing down. Early data from the National Institutes of Health (NIH), reported in Science News, showed a loss of THC receptors in the brains of Huntington’s sufferers.

Queen Elizabeth believed that marijuana tamed her menstrual cramps back in the 16th Century, but there is no clinical and little anecdotal evidence to support this notion. Perhaps the anti-anxiety and mood elevating effects associated with marijuana are useful for menstrual irritation and mood swings, just as they are sometimes perceived to be useful by those suffering from depression.

The typical joint rolled in paper contains roughly 0.5 grams of plant matter, of which anywhere from 1 to 15 per cent is THC. THC content varies widely because some genetic strains of cannabis are more potent than others. This fact has led to intense debate in the United Kingdom over the issue of so-called “Skunk” marijuana. Skunk is not a new, lethally potent form of pot, but rather a shorthand term for describing one of several strains of strong, aromatic female marijuana plants. Most of the potent forms of marijuana for sale are hybrids resulting from cross-pollination of various strains. Of itself, “Skunk” marijuana is no more or less dangerous than other potent and popular varietals, such as “White Widow” or "Hawaiian Haze."

The half-life of marijuana is fairly short—about 50 hours for inexperienced users, and about half that for experienced users. However, THC and its metabolites are fat soluble, and are therefore easily stored in fatty tissue. Other drugs clear the system much more efficiently. The marijuana high may be history, but the metabolites live on--for up to 30 days. Blood tests can confirm THC in the body, but cannot reliably determine how recently the marijuana was smoked. There is no marijuana analysis kit comparable to the Breathalyzer test for alcohol. Drivers under the influence of cannabis may suffer some perceptual impairment. They tend to drive more slowly and take fewer risks, compared to drivers under the influence of alcohol. Possibly, cannabis smokers are hyperaware of the modest motor impairments they exhibit under the influence. Heavy drinkers are often unaware that there is anything wrong with their driving at all, as their sometimes-vociferous arguments with police officers and state troopers can attest.

As with cigarettes, chronic pot smoking can lead to chronic bronchitis. We don’t know for certain whether heavy marijuana use causes lung cancer, but it seems safe to assume that smoking vegetable matter in any form is not compatible with the long-term health of lung tissue. Patients with risk factors for cardiovascular disease are well advised not to smoke anything. Marijuana smoking can raise the resting heart rate as much as 30 per cent in a matter of minutes, and while there is no present evidence of harmful effects from this, we will have to monitor the situation more closely as pot-smoking and former pot-smoking Baby Boomers enter their cardiovascular disease years.

Other patients for whom marijuana is definitely not indicated include those suffering from respiratory disorders--asthma, emphysema, or bronchitis. In addition, schizophrenics or anyone at genetic risk for schizophrenia should shun pot, as it has been known to exacerbate or precipitate schizophrenic episodes—though it does not, as is commonly rumored, cause schizophrenia.

The evidence for significant impairment of cognitive function is equivocal—heavy marijuana use does not, like alcohol, result in gross structural brain damage. Numerous studies have addressed the possibility of subtler impairments in memory, attention, and the retention of new information. The extent to which such alterations are transient as opposed to long term is still under scientific debate.

Cannabis augments the effects of morphine in animal studies, thus allowing for a lower dose of opiates. Pain relief may be a primary attribute of anandamide—the brain’s own THC. Rats given the drug were less sensitive to pain than their non-drugged counterparts, as detailed in the Proceedings of the National Academy of Sciences. Drug companies may have closed the book on marijuana spin-offs too early. It would not be surprising if pills to selectively increase the amount of anandamide in the brain will one day augment or offer an alternative to existing anti-anxiety medications or pain relievers. On the other hand, a substance that blocks anandamide might find use as an agent to help combat memory loss.

Graphic: http://www.seedsman.com/en/health

For more, see: The Chemical Carousel: What Science Tells Us About Beating Addiction © Dirk Hanson 2008, 2009.

Related Posts: Anandamide: The Brain's Own Marijuana

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Anandamide: The Brain’s Own Marijuana

Anxiety and the THC receptor.

Several years ago, molecular biologists identified the elusive brain receptor where THC, the active ingredient in marijuana, did its work. Shortly after that discovery, researchers at Hebrew University in Jerusalem identified the body’s own form of THC, which sticks to the same receptors, in pulverized pig brains. They christened the internally manufactured substance “anandamide,” after the Sanskrit ananda, or bliss.

Anandamide has a streamlined three-dimensional structure that THC mimics, and both molecules slipped easily across the blood-brain barrier. Anandamide is a short-lived, fragile molecule, and does not produce a dramatic natural high, unlike a surge of endorphins, or dopamine—or the THC in a joint. In 2001, researchers at the Keck Center for Integrative Neuroscience at the University of California-San Francisco found evidence that THC may perform a signaling function in neurons containing GABA and glutamate. It appears that marijuana increases dopamine and serotonin levels through the intermediary activation of opiate and GABA receptors.

However, anandamide has a number of other effects, particularly on movement and cognition. Because of this, the “bliss molecule” moniker is a bit misleading. THC and its organic cousin make an impressive triple play in the brain: They effect movement through receptors in the basal ganglia, they alter sensory perception through receptors in the cerebral cortex, and they impact memory by means of receptors in the hippocampus.

It was left for animal physiologist Gary Weesner of the U.S. Department of Agriculture (USDA) to answer the burning question: “How do pigs use their anandamide?” While studying the possibility of using anandamide as a sedative for animals, Dr. Weesner discovered that pigs treated with anandamide tended to have lower body temperature, slower respiration, and less movement—all of which are signs of a calmer porcine state of mind.

So much for pigs. What does anandamide do in the human brain? For starters, we can look toward those controversial indications for which marijuana is already being prescribed: anxiety relief, appetite enhancement (compounds similar to anandamide have been discovered in dark chocolate) suppression of nausea, relief from the symptoms of glaucoma, and amelioration of certain kinds of pain. U.S. pharmaceutical houses, Pfizer in particular, worked with THC for years, seeking profitable patents. But Pfizer never succeeded in separating out the various pharmacological effects of marijuana, and in the end, their efforts were limited to the manufacture of synthetic THC.

Ten years ago, scientists at the National Institute of Mental Health (NIMH) uncovered preliminary evidence that cannabis may afford a measure of protection from brain cell damage due to stroke. An Israeli pharmaceutical company announced plans to test a synthetic marijuana derivative for the treatment of strokes and brain injury. There are few effective treatments for stroke, the third leading killer in the United States.

The question of short-term memory loss under the influence of pot appears to have been answered by related research. Findings from the Neurosciences Institute in San Diego show that cannabinoids are capable of blocking new memory formation in animal brain tissue. If anandamide receptors trigger a form of forgetfulness, this may be part of the brain’s system of filtering out unimportant or unpleasant memories—a vital function, without which we would all be overwhelmed by irrelevant and unprovoked memories at every turn.

For example, the brain’s own cannabis may help women “forget” the pain and stress of childbearing, allowing them to concentrate on the immediate needs of the newborn. Other animal research suggests that the uterus grows anandamide receptors in heavy concentrations before embryo implantation. Still other studies show that newborn kittens and monkeys have more marijuana receptors in the cortex than adults do, so it is possible that anandamide may play some role in setting up the development of cortical function in infants.

For more, see earlier posts:
Marijuana Withdrawal
Is Marijuana Addictive?

Photo Credit: National Institute of Drug Abuse

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U.K Considers Tougher Pot Law

Health officials claim 500 hospitalizations per week.

In a reversal of previous policy, Prime Minister Gordon Brown signaled his likely approval of a move to stiffen marijuana enforcement by upgrading cannabis to so-called Class B drug status. If approved by Brown’s Advisory Council on the Misuse of Drugs, the reclassification would mean a prison term of up to five years for possession of marijuana.

Meanwhile, the London Daily Telegraph, citing high-level health authorities, claimed that official figures showed a 50 per cent increase in the number of people requiring medical attention after cannabis use. “Almost 500 adults and children are treated in hospitals and clinics every week for the effects of cannabis,” the article claimed.

The Telegraph went on to assert that the figures “proved Labour’s decision to reclassify cannabis in January 2004, which made the penalties for its possession less severe, was badly mistaken and had sent out the wrong signals about it being a ‘soft’ drug.”

Previously, the British government under Tony Blair had downgraded cannabis to a Class C drug in 2004, putting it in the same group with steroids and prescription antidepressants. Class B includes amphetamines and cocaine.

Home Secretary Jacqui Smith, in a letter to the Advisory Council, said that “there is real public concern about the potential mental health effects of cannabis use, in particular the use of stronger forms of the drug, commonly known as skunk.”

Last July, Mr. Brown explained his intentions: “Why I want to upgrade cannabis and make it more a drug that people worry about is that we don’t want to send out a message, just like with alcohol, to teenagers that we accept these things.”

DrugScope, a British drug policy organization, sent a letter to the Telegraph opposing the move, charging that the Telegraph had misrepresented figures given out by the Minister of State for Public Health. “We have ascertained that the figures supplied by the Minister do not relate to actual hospital admissions,” said the DrugScope letter. “The figures instead relate to those who have come forward to community-based drug treatment services seeking some form of help, advice or treatment relating to their use of cannabis.” Drugscope’s analysis of the figures yielded a national figure of 14 hospital admissions per week. “This is 14 admissions too many,” DrugScope wrote, “but still way below the figure quoted.”

The debate harkens back to a mental health story run by the London Daily Mail in August, which claimed that smoking a single joint of marijuana increases the risk of developing schizophrenia by 41 per cent—an erroneous statistic that was also hotly contested by various U.K. drug experts.

The tighter pot laws envisioned by the Prime Minister dovetail neatly with the current emphasis by U.S. Drug Czar John P. Walters on teenage cannabis use--a stance that has enraged many U.S. officials, including Iowa Republican Senator Charles Grassley, according to a recent, well-researched article in Rolling Stone. “What I’ve never understood,” said Grassley, “is why they took marijuana so much more seriously that methamphetamine, when methamphetamine is a much more serious drug.”

Harm Reduction: The Dutch Experience

Does marijuana decriminalization work?

Decriminalization of certain drug offenses is one of the goals of a loosely organized movement called harm reduction. While it neither ignores the dangers of addictive drugs, nor advocates their use, harm reduction, as practiced by organizations like the Harm Reduction Coalition, is a limited step that calls for making distinctions between major and minor classes of drug crimes. Above all, it is a practical approach.

According to the International Harm Reduction Association: “In many countries with zero tolerance drug policies, funding for drug law enforcement is five to six times greater than funding for prevention and treatment.” In place of that scenario, harm reduction strategies aim for the creation of non-coercive, community-based recovery programs and resources for drug users. The association defines harm reduction as follows: “Policies and programs which attempt primarily to reduce the adverse health, social, and economic consequences of mood altering substances to individual drug users, their families and their communities.”

Harm reduction strategies do not call upon the government to eradicate the drug problem. Nor would they ultimately lead to cocaine and heroin being sold in government-owned versions of mom-and-pop drugstores. It calls for judgment and discrimination on the part of law enforcement agencies, judges, juries, lawyers, and everyday citizens. The controversial Dutch experiment with harm reduction is often the focal point of such discussions. In 1976, the Dutch made a misdemeanor out of the sale of up to one ounce of cannabis. In the Netherlands, possession of marijuana and heroin is illegal, but there are certain well-defined exceptions, such as the Amsterdam coffee houses, where marijuana and hashish may be freely purchased and consumed. The coffee houses pay taxes on their marijuana sales, just as they do with sales of beer.

The price of marijuana and hashish available in the shops is reasonably low, which cuts back on the need to commit crimes in order to pay for it, and lowers the profits available to street dealers. “If we kept chasing grass or hashish, the dealers would go underground, and that would be dangerous,” a senior Dutch police officer told The Economist (sub. required).

The Dutch officer insisted that the Dutch do not intend to reverse course, as happened in Alaska. “The Americans offer us big money to fight the war on drugs their way. We do not say that our way is right for them, but we are sure it is right for us. We don’t want their help.”

Dutch police still possess strong enforcement powers when it comes to hard drugs, but they have been instructed to view the issue as a public health problem. Heroin addicts are tolerated, but steered in the direction of treatment. By some accounts, 75 per cent of Dutch heroin addicts are involved in one treatment program or another. Local officials complain that some of their drug problem can be traced to a flood of young people coming in from other countries where stricter drug laws are in force.

The Dutch experiment rests on the belief that drug addiction is a medical problem, and that medical problems cannot be solved within the structure of the criminal justice system. “The lifetime prevalence of cannabis use in the Netherlands for 10- to 18-year-olds is 4.2 per cent,” Science (sub. required) reported, “compared with the U.S. High School Survey figure of approximately 30 per cent.”

Marijuana Withdrawal

For Some Users, Cannabis Can Be Fiercely Addictive.

(Note: more than 1200 comments below)

See Also:
Is Marijuana Addictive? (>143 posts)
Marijuana Withdrawal Revisited. (>108posts).
Feds Fund Study of Marijuana Withdrawal. (>39 posts)

For a minority of marijuana users, commonly estimated at 10 per cent, the use of pot can become uncontrollable, as with any other addictive drug. Addiction to marijuana is frequently submerged in the welter of polyaddictions common to active addicts. The withdrawal rigors of, say, alcohol or heroin tend to drown out the subtler, more psychological manifestations of cannabis withdrawal.

What has emerged in the past ten years is a profile of marijuana withdrawal, where none existed before. The syndrome is marked by irritability, restlessness, generalized anxiety, hostility, depression, difficulty sleeping, excessive sweating, loose stools, loss of appetite, and a general “blah” feeling. Many patients complain of feeling like they have a low-grade flu, and they describe a psychological state of existential uncertainty—“inner unrest,” as one researcher calls it.

The most common marijuana withdrawal symptom is low-grade anxiety. Anxiety of this sort has a firm biochemical substrate, produced by withdrawal, craving, and detoxification from almost all drugs of abuse. It is not the kind of anxiety that can be deflected by forcibly thinking “happy thoughts,” or staying busy all the time.

A peptide known as corticotrophin-releasing factor (CRF) is linked to this kind of anxiety. Neurologists at the Scripps Research Institute in La Jolla, California, noting that anxiety is the universal keynote symptom of drug and alcohol withdrawal, started looking at the release of CRF in the amygdala. After documenting elevated CRF levels in rat brains during alcohol, heroin, and cocaine withdrawal, the researchers injected synthetic THC into 50 rats once a day for two weeks. (For better or worse, this is how many of the animal models simulate heavy, long-term pot use in humans). Then they gave the rats a THC agonist that bound to the THC receptors without activating them. The result: The rats exhibited withdrawal symptoms such as compulsive grooming and teeth chattering—the kinds of stress behaviors rats engage in when they are kicking the habit. In the end, when the scientists measured CRF levels in the amygdalas of the animals, they found three times as much CRF, compared to animal control groups.

While subtler and more drawn out, the process of kicking marijuana can now be demonstrated as a neurochemical fact. It appears that marijuana increases dopamine and serotonin levels through the intermediary activation of opiate and GABA receptors. Drugs like naloxone, which block heroin, might have a role to play in marijuana detoxification.

As Dr. DeChiara of the Italian research team suggested in Science, “this overlap in the effects of THC and opiates on the reward pathway may provide a biological basis for the controversial ‘gateway hypothesis,’ in which smoking marijuana is thought to cause some people to abuse harder drugs.” America's second favorite drug, De Chiara suggests, may prime the brain to seek substances like heroin. In rebuttal, marijuana experts Lester Grinspoon and James Bakalar of Harvard Medical school have protested this resumed interest in the gateway theory, pointing out that if substances that boost dopamine in the reward pathways are gateways to heroin use, than we had better add chocolate, sex, and alcohol to the list.

In the end, what surprised many observers was simply that the idea of treatment for marijuana dependence seemed to appeal to such a large number of people. The Addiction Research Foundation in Toronto has reported that even brief interventions, in the form of support group sessions, can be useful for addicted pot smokers.

In 2005, an article in the American Journal of Psychiatry concluded that, for patients recently out of rehab, “Postdischarge cannabis use substantially and significantly increased the hazard of first use of any substance and strongly reduced the likelihood of stable remission from use of any substance.”

A selected bibliography of science journal references can be found HERE.

See also:
Marijuana Withdrawal Rivals Nicotine
Marijuana Withdrawal Revisited
Feds Fund Study of Marijuana Withdrawal

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Is Marijuana Addictive?

The argument continues.

For more, see Marijuana Withdrawal.
See also Marijuana Withdrawal Revisited

Marijuana may not be a life-threatening drug, but is it an addictive one?

There is little evidence in animal models for tolerance and withdrawal, the classic determinants of addiction. For at least four decades, million of Americans have used marijuana without clear evidence of a withdrawal syndrome. Most recreational marijuana users find that too much pot in one day makes them lethargic and uncomfortable. Self-proclaimed marijuana addicts, on the other hand, report that pot energizes them, calms them down when they are nervous, or otherwise allows them to function normally. They feel lethargic and uncomfortable without it. Heavy marijuana users claim that tolerance does build. And when they withdraw from use, they report strong cravings.

Marijuana is the odd drug out. To the early researchers, it did not look like it should be addictive. Nevertheless, for some people, it is. Recently, a group of Italian researchers succeeded in demonstrating that THC releases dopamine along the reward pathway, like all other drugs of abuse. Some of the mystery of cannabis had been resolved by the end of the 1990s, after researchers had demonstrated that marijuana definitely increased dopamine activity in the ventral tegmental area. Some of the effects of pot are produced the old-fashioned way after all--through alterations along the limbic reward pathway.

By the year 2000, more than 100,000 Americans a year were seeking treatment for marijuana dependency, by some estimates.

A report prepared for Australia’s National Task Force on Cannabis put the matter straightforwardly:

There is good experimental evidence that chronic heavy cannabis users can develop tolerance to its subjective and cardiovascular effects, and there is suggestive evidence that some users may experience a withdrawal syndrome on the abrupt cessation of cannabis use. There is clinical and epidemiological evidence that some heavy cannabis users experience problems in controlling their cannabis use, and continue to use the drug despite experiencing adverse personal consequences of use. There is limited evidence in favour of a cannabis dependence syndrome analogous to the alcohol dependence syndrome. If the estimates of the community prevalence of drug dependence provided by the Epidemiologic Catchment Area Study are correct, then cannabis dependence is the most common form of dependence on illicit drugs.

While everyone was busy arguing over whether marijuana produced a classic withdrawal profile, a minority of users, commonly estimated at 10 per cent, found themselves unable to control their use of pot. Addiction to marijuana had been submerged in the welter of polyaddictions common to active addicts. The withdrawal rigors of, say, alcohol or heroin would drown out the subtler, more psychological manifestations of marijuana withdrawal.

What has emerged is a profile of marijuana withdrawal, where none existed before. The syndrome is marked by irritability, restlessness, generalized anxiety, hostility, depression, difficulty sleeping, excessive sweating, loose stools, loss of appetite, and a general “blah” feeling. Many patients complain of feeling like they have a low-grade flu, and they describe a psychological state of existential uncertainty—“inner unrest,” as one researcher calls it.

The most common marijuana withdrawal symptom is low-grade anxiety. Anxiety of this sort has a firm biochemical substrate, produced by withdrawal, craving, and detoxification from almost all drugs of abuse. It is not the kind of anxiety that can be deflected by forcibly thinking “happy thoughts,” or staying busy all the time. A peptide known as corticotrophin-releasing factor (CRF) is linked to this kind of anxiety.

Neurologists at the Scripps Research Institute in La Jolla, California, noting that anxiety is the universal keynote symptom of drug and alcohol withdrawal, started looking at the release of CRF in the amygdala. After documenting elevated CRF levels in rat brains during alcohol, heroin, and cocaine withdrawal, the researchers injected synthetic THC into 50 rats once a day for two weeks. (For better or worse, this is how many of the animal models simulate heavy, long-term pot use in humans). Then they gave the rats a THC agonist that bound to the THC receptors without activating them. The result: The rats exhibited withdrawal symptoms such as compulsive grooming and teeth chattering—the kinds of stress behaviors rats engage in when they are kicking the habit. In the end, when the scientists measured CRF levels in the amygdalas of the animals, they found three times as much CRF, compared to animal control groups.

While subtler and more drawn out, the process of kicking marijuana can now be demonstrated as a neurochemical fact. It appears that marijuana increases dopamine and serotonin levels through the intermediary activation of opiate and GABA receptors. Drugs like naloxone, which block heroin, might have a role to play in marijuana detoxification.

In the end, what surprised many observers was simply that the idea of treatment for marijuana dependence seemed to appeal to such a large number of people. The Addiction Research Foundation in Toronto has reported that even brief interventions, in the form of support group sessions, can be useful for addicted pot smokers.

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

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