The Year in Drugs

Top Posts at Addiction Inbox.

By the look of it, readers had marijuana on their minds in 2012. Of the posts at Addiction Inbox with the highest number of page views, an overwhelming majority are concerned with marijuana, and specifically, with marijuana addiction, withdrawal, and brain chemistry. Of the 9 most heavily trafficked posts of the year, only one involved alcohol. Readers were also interested in the safety of e-cigarettes, and the mysteries of neurotransmitters like serotonin and dopamine. Happily, all the top posts were patently science-oriented articles.

See you in the New Year.

•  Marijuana Withdrawal

For Some Users, Cannabis Can Be Fiercely Addictive.

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.

•  Serotonin and Dopamine: A Primer

The Molecules of Reward

Serotonin and dopamine are part of a group of compounds called biogenic amines. In addition to serotonin and dopamine, the amines include noradrenaline, acetylcholine, and histamine. This class of chemical messengers is produced, in turn, from basic amino acids like tyrosine, tryptophan, and choline.

•  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.

• 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.

•  The Mysteries of the Blunt

Why do so many smokers combine tobacco with marijuana?

People who smoke a combination of tobacco and marijuana, a common practice overseas for years, and increasingly popular here in the form of “blunts,” may be reacting to ResearchBlogging.orgsome 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.

•  Are E-Cigarettes a Good Idea or a Bad Idea?

A group of nicotine researchers argue for an alternative.

Electronic cigarettes are here to stay. If you're not familiar with them, e-cigarettes are designed to look exactly like conventional cigarettes, but they use batteries to convert liquid nicotine into a fine, heated mist that is absorbed by the lungs. Last summer, even though the FDA insisted on referring to e-cigarettes as “untested drug delivery systems,” Dr. Neal Benowitz of the University of California in San Francisco--a prominent nicotine researcher for many years--called e-cigarettes “an advancement that the field has been waiting for.”

•  Cannabis Receptors and the “Runner’s High”

Maybe it isn't endorphins after all.

A perennial favorite, the runner’s high post shows what long-distance running and marijuana smoking have in common. Quite possibly, more than you’d think. A growing body of research suggests that the runner’s high and the cannabis high are more similar than previously imagined….Endocannabinoids—the body’s internal cannabis—“seem to contribute to the motivational aspects of voluntary running in rodents.” Knockout mice lacking the cannabinioid CB1 receptor, it turns out, spend less time wheel running than normal mice. 

• Topamax for Alcoholism: A Closer Look

Epilepsy drug gains ground, draws fire as newest anti-craving pill.

A drug for seizure disorders and migraines continues to show promise as an anti-craving drug for alcoholism, the third leading cause of death in America, the Journal of the American Medical Association (JAMA) reported in its current issue.

•  Is Marijuana Addictive?

The argument continues.

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.


Graphics Credit:  http://1.bp.blogspot.com (Creative Commons)

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/

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

Marijuana Q & A

My interview with AllTreatment Blog.

Denny Chapin, Managing Editor of AllTreatment.com, was recently invited to participate in an extended debate over marijuana withdrawal at the Drug WarRant blog site. I followed that debate with interest, due to the unusually high volume of responses to my own post on that subject.

Now Denny has kindly provided me the opportunity to offer my own views on a set of questions about cannabis use and cannabis dependency. The complete interview can be read at the AllTreatment site HERE.

Photo credit: http://www.medicalmarijuana.co.cc

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.

Marijuana Withdrawal: A Survey of Symptoms (Part 1)

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.]

(See also Marijuana Withdrawal Post)

More than 14 million Americans smoke marijuana regularly, making it the most commonly used illicit drug in America. In 2006, marijuana was the only drug used by 52.8 percent of illegal drug users (U.S. Department of Health and Human Services, 2006).

Over the past 15 years, as addiction researchers have been busily mapping out the chemical alterations in the human nervous system caused by alcohol, cocaine, nicotine, heroin, and tranquilizers, America’s most popular illegal drug has remained largely a scientific mystery. Marijuana, the drug millions of Americans have been using regularly for years, is the least studied drug of all.

Why has cannabis research lagged behind that of other drugs of abuse? For decades, the prevailing belief among users and clinical researchers alike was that marijuana did not produce dependency and therefore could not be responsible for major withdrawal symptoms. This thinking is based, quite understandably, on the widespread observation that most marijuana users do not have difficulty going without marijuana, either by choice or by necessity. However, marijuana withdrawal effects are 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 manifestations of cannabis withdrawal. As Barbara Mason, director of the Laboratory of Clinical Psychopharmacology at Scripps Research Institute, has explained: “People are deciding every day whether to use or not to use marijuana, for medical purposes or otherwise, and there is little scientific information to advise this decision” (2008).

Marijuana withdrawal, which typically affects only heavy smokers, has not been well characterized by the research community. Until recently, there was scant evidence in animal models for marijuana tolerance and withdrawal, the classic determinants of addiction. Now, however, several researchers have identified the existence of symptoms brought on by the abrupt discontinuation of regular marijuana use in both animal and human studies (de Fonseca et al., 1997, p. 2050). A growing body of evidence supports the existence of a clinically significant marijuana withdrawal syndrome in a subset of marijuana smokers. The syndrome is marked by irritability, restlessness, generalized anxiety, hostility, depression, difficulty sleeping, excessive sweating, loose stools, loss of appetite, a general “blah” feeling, and a mental state that has been described as “inner unrest.”

Recent clinical research, combined with anecdotal field reports collected by the author, demonstrate the existence of marijuana withdrawal and the consistency of the most common symptoms of withdrawal and detoxification.

Background

In 1992, molecular biologists identified the elusive brain receptor where THC, the primary 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 uses the same CB1 receptors as THC. They christened the internally manufactured substance anandamide, after the Sanskrit ananda, or “bliss” (Fackelmann, 1993).

Anandamide has a streamlined three-dimensional structure that THC mimics. Both molecules slip easily through the blood brain barrier. Some of the mystery of marijuana’s effects was resolved after researchers demonstrated that marijuana definitely increased dopamine activity in the limbic area of the brain. Tanda, Pontieri, and Di Chiara demonstrated that dopamine levels in the nucleus accumbens doubled when rats received an infusion of THC (1997, p. 2048). It appears that marijuana raises dopamine and serotonin levels through the intermediary activation of opiate and GABA receptors (Wilson & Nicoll, 2001, p. 588). THC may perform a signaling function in neurons containing GABA and glutamate.

THC and its organic cousin, anandamide, 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 is clear that some of the effects of cannabis are produced in much the same way as the effects of other addictive drugs—by means of neurotransmitter alterations along the limbic system’s reward pathway.

A great deal of the early research was marred by inconsistent findings and differing definitions of addiction and withdrawal. 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. Heavy marijuana users claim that tolerance does build. And when they withdraw from use, many report strong cravings.

Work by Jones, Benowitz, and Herning had helped establish certain baseline symptoms—irritability, insomnia, and lack of appetite—as early as 1981 (p. 143). Studies by Budney, Novy, and Hughes in 1999 further outlined the syndrome in heavy daily marijuana smokers (p. 1311). But the abstinence effects were often inconsistent, and frequently hard to measure. Moreover, their clinical relevance was not always evident.

For marijuana withdrawal to be considered a clinical fact, several criteria had to be met. First, the typically transient pattern of withdrawal effects must be distinguishable from rebound effects. (A rebound effect is defined as the reappearance of a preexisting symptom, and is thus not considered a true withdrawal effect.) In addition, the symptoms must occur reliably, as demonstrated by comprehensive prospective studies (Budney, Hughes, Moore, & Vandrey, 2004, p. 1970). The symptoms under consideration must also be considered clinically significant. Finally, there needs to be a clear and repeatable timeline in evidence for the withdrawal effects.

It has been suggested that the reported symptoms of abrupt marijuana cessation do not rise to the level of withdrawal typically associated with drug detox. It is now possible to lay out the neurochemical basis of marijuana withdrawal, and to demonstrate that marijuana acts on the brain in a fashion similar to other addictive drugs.

There is solid experimental evidence that chronic, heavy cannabis users develop tolerance to its subjective and cardiovascular effects. “In summary,” Budney et al. write, “cannabis withdrawal effects clearly occur in the majority of heavy, daily users” (2004, p. 1974). As a rough estimate, approximately 10 percent of marijuana users are at risk for dependence and withdrawal, the classic determinants of drug addiction (Joy, Watson, & Benson, 1999, p. 92). 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 (Hall, Solowij, & Lemon, 1999). Moreover, there is strong clinical evidence that some users experience a withdrawal syndrome upon the abrupt cessation of cannabis use. The timeline is similar to withdrawal from other addictive drugs.

In 2004, a group at the University of Vermont, funded by the National Institute of Drug Abuse (NIDA), undertook a critical review of all major relevant studies of the validity and clinical significance of marijuana withdrawal (Budney et al., p. 1967). The review of studies demonstrated with certainty that there are people with a propensity for heavy marijuana use who suffer a clearly delineated, verifiable, and frequently vivid set of withdrawal symptoms when they try to quit. One of the most striking pieces of evidence for this is the similarity of symptom sets emerging from the clinical studies to date. The most common “reliable and clinically significant” effects of abrupt withdrawal in heavy pot smokers, according to the University of Vermont research group, included “severity of craving and sleep difficulty, decreased appetite, and increased aggression, anger and irritability” (Budney, Hughes, Moore, & Novy, 2001, p. 917; Kouri, 2002, p. 30).

As another study author concluded: “Marijuana withdrawal doesn’t include dramatic physical symptoms such as the pain, nausea, heavy sweating, and cramps associated with opiate withdrawal. Nevertheless, the symptoms of marijuana withdrawal appear clinically significant” (Zickler, 2002).

A recent comprehensive outpatient study (Kouri & Pope, 2000, p. 483) with prewithdrawal baselines showed greater levels of anxiety, negative mood, physical discomfort, and decreased appetite during abstinence but not at baseline, compared with two control groups. Moreover, in a “home environment” study, researchers worked with marijuana users who provided self-ratings during marijuana withdrawal; these users smoked an average of 3.6 times daily, did not use other drugs or abuse alcohol, and were free of major psychiatric disorders. The same symptoms predominated, and onset of symptoms occurred reliably within 48 hours of cessation. Moreover, “telephone interviews with collateral observers living with the participants confirmed participants’ reports of increased irritability, aggression, and restlessness during abstinence. . . . [T]he validation of symptoms by home-based observers suggested that the effects were of a clinically significant magnitude” (Budney et al., 2004, p. 1971).

Other studies by Budney and colleagues expanded on the list of symptoms that changed significantly from baseline during withdrawal: “anger and aggression, decreased appetite, irritability, nervousness, restlessness, shakiness, sleep difficulty, stomach pain, strange dreams, sweating, and weight loss” (2003, p. 393; 2004, p. 1972). Although most effects were transient, generally lasting no more than two weeks, “strange dreams and sleep difficulties showed significant elevations throughout the study” (2003). Budney et al. conclude that, since most symptoms returned to baseline levels in the former users, “these findings were not rebound effects indicative of symptoms that existed before the use of cannabis” (2004, p. 1972).

More recent studies by Haney and others “controlled for potential confounders by using placebo conditions and excluding persons who abused other substances, had an active psychiatric disorder, or were taking psychoactive medication” ().

Overall, the research cited above confirms that the most common marijuana withdrawal symptom is low-grade anxiety and dysphoria. Anxiety of this sort has a firm biochemical substrate. A peptide known as corticotrophin-releasing factor (CRF) is primarily responsible. Neurologists at the Scripps Research Institute in La Jolla, California, found that CRF levels in the amygdalas of animals in marijuana withdrawal were as much as three times higher than the levels found in animal control groups (Wickelgren, 1997, p. 1967). Long-term marijuana use alters the function of CRF in the limbic system in a manner similar to other addictive drugs (de Fonseca et al., 1997, p. 2051). (CRF receptors in the amygdala also play a direct role in alcohol withdrawal.)

Method

Personal observations and selected case histories of frequent marijuana users were gathered from anonymous, unedited comments posted on a blog site maintained by the author. Punctuation, capitalization, and spelling have been normalized in the excerpts included here. Most of the people who have posted comments thus far (more than 100) arrived at the site by means of the search term marijuana withdrawal. This may indicate that a large number of posters are heavy smokers seeking information about abstinence symptoms. The popularity of this search phrase on the Google search engine seems to suggest an interest in, and a need for, scientific information about marijuana withdrawal.

What has surprised many observers is that the idea of treatment for marijuana dependence seems to appeal to such a large and diverse group of people. NIDA has been able to find a cohort of withdrawal-prone smokers with relative ease. According to the principal investigator of one NIDA marijuana study, “We had no difficulty recruiting dozens of people between the ages of 30 and 55 who have smoked marijuana at least 5,000 times. A simple ad in the paper generated hundreds of phone calls from such people” (NIDA, 1999). This would be roughly equivalent to 14 years of daily pot smoking.

Comments gathered from anonymous users at an open Web forum created for the discussion of marijuana withdrawal symptoms cannot be controlled for confounding variables such as other addictions or psychological disorders. The comment section of the Web site is open to anyone. What such surveys can accomplish, however, is the demonstration of parallels, or lack of them, between findings in an experimental setting and anecdotal reports from the field. Survey studies cannot offer indisputable proof. Nonetheless, when combined with the results of formal clinical studies, such surveys offer a window into real-world experience, thus complementing the growing scientific data concerning marijuana withdrawal syndrome.

The comments were generated in large part by heavy, regular smokers who either recognized or have begun to recognize in themselves an addictive propensity toward marijuana. As a group, they have great difficulty—and suffer similar symptoms—whenever, and for whatever reason, they choose to abstain.

Perhaps, most important, the present survey adds to the growing documentation of the contention that withdrawal symptoms are a frequent cause of relapse in marijuana smokers attempting to achieve abstinence.

Cont. in Part 2.

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, 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. Retrieved February 27, 2008, from http://archpsyc.ama assn.org/cgi/content/full/58/10/917?cknck

Budney, A. 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. Retrieved April 21, 2008, from http://ajp.psychiatryonline.org/cgi/content/full/161/11/1967

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., 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. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/11239727

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. Retrieved April 27, 2008, from http://www.jneurosci.org/cgi/content/abstract/21/24/9867

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.

Fackelmann, K. A. (1993, February 6). Marijuana and the brain: Scientists discover the brain’s own THC-delta-9-tetrahydrocannabinol. Science News. Retrieved March 28, 2008, from http://findarticles.com/p/articles/mi_m1200/is_n6_v143/ai_13434805/pg_1

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. Retrieved February 3, 2008, from http://www.druglibrary.org/schaffer/hemp/medical/home.htm

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, C. L., Ward, A. 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.

Hanson, D. (2007, October 17). Addiction inbox: Marijuana withdrawal. Retrieved May 3, 2008, from http://addiction-dirkh.blogspot.com/2007/10/marijuana-withdrawal.html

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. Retrieved April 14, 2008, from http://www.ncbi.nlm.nih.gov/sites/entrez

Joy, J. E., Watson, S. J., & Benson, J. A. (1999). Marijuana and medicine: Assessing the science base. Institute of Medicine, Division of Neuroscience and Behavioral Health. Washington, DC: National Academy Press. Retrieved March 5, 2008, from http://www.nap.edu/html/marimed/

Kouri, E. M. (2002, February 1). Does marijuana withdrawal syndrome exist? Psychiatric Times, 19(2). Retrieved March 17, 2008, from http://www.psychiatrictimes.com/display/article/10168/54701?pageNumber3

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. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/

Lichtman, A. H., & Martin, B. R. (2002). Marijuana withdrawal syndrome in the animal model. Journal of Clinical Pharmacology, 42, 20s–27s.

Mason, B. (2008, March 15). North County Times.

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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. Retrieved March 16, 2008, from http://www.nctimes.com/articles/2008/03/15/news/sandiego/16_02_343_14_08.txt

Somers, T. (2008, March 14). Study aims to clear haze surrounding pot addiction. San Diego Union-Tribune. Retrieved March 16, 2008, from http://www.signonsandiego.com/news/science/20080314–9999–1n14dope.html

Tanda, G., Pontieri, F. E., & Di Chiara, G. (1997, June 27). Cannabinoid and heroin activation of mesolimbic dopamine transmission by a common 1 opioid receptor mechanism. Science, 276, 2048–2050.

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Vandrey, R. G., Budney, A. J., Hughes, J. R., & Liguori, A. (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.

Photo Credit: http://hubpages.com/

Smoke Alarm

The Cannabis and Tobacco Education Initiative.

My British friend James Langton, author of No Need For Weed, who maintains the excellent web site Clearhead for people with marijuana abuse problems, has launched a new site called Smoke Alarm.

The new venture is a non-profit company dedicated to the proposition of “offering credible information to the estimated 3 million people who regularly smoke tobacco joints here in the UK. We do this by directly educating through schools and colleges as well as indirectly through tobacco cessation professionals, drug agencies, and youth services.”

James Langton is in a unique position to help smokers in Europe, where the preferred drug delivery method for nicotine and marijuana is a joint of marijuana and tobacco rolled together—a smoking method that has never really caught on in the U.S. This preference for combining the two smokes into a “tobacco joint” creates “a powerfully addictive carcinogenic cocktail,” Langton writes on the new site. “Cannabis and tobacco are intimately connected and although the science of nicotine addiction is well understood, much less is known about how to help cannabis smokers with the psychological and physiological aspects of their dependency, and how the two substances interrelate to compound the difficulties in quitting either or both, together or separately.”

Langton’s book, No Need For Weed: Understanding and Breaking Cannabis Dependency, published by Hindsight Press, chronicles the author’s 30 years of experience as an addicted marijuana smoker, and explores the thoughts and difficulties of others who have suffered various degrees of marijuana dependency (See my support site on Marijuana Withdrawal).

“Cannabis continues to be an extremely popular drug with young people in the United Kingdom, and the fact that 44% of fifteen and sixteen year olds admitted to using the drug at some point in their lives when questioned for the 2008 United Nations International Narcotics Control Board report should not come as a surprise,” Langton writes. “Many young cannabis smokers do not consider themselves to be nicotine addicted simply because they mix their cannabis with tobacco. However, it's when the supply of cannabis is curtailed or they make an attempt to quit the drug that the nicotine pull gains dominance. This dynamic can set up a life-time nicotine cannabis relationship that remains one of the hardest for adult drug users to break.”

addiction drugs smoking nicotine

Marijuana Panic Revisited

U.K. journal casts doubt on psychosis connection.

In May of this year, The University College of London reports that different strains of marijuana cause different types of psychological maladies. Shortly thereafter, 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. (See "U.K. Marijuana Panic Continues"). And in August, a mental health story run by the London Daily Mail claimed that smoking a single joint of marijuana increased the risk of developing schizophrenia by 41 per cent—an erroneous statistic that was also hotly contested by various U.K. drug experts. (See "Media Suffers Attack of Cannabis Psychosis").

Now comes a review article from the British Journal of Psychiatry, published by the Royal College of Psychiatrists, strongly suggesting that the odds of an association between cannabis and psychosis is “low.”

A group of drug experts and psychiatrists, including scientists from the University of Bristol, Imperial College London, Cambridge University, and Cardiff University undertook to “systematically review the evidence pertaining to whether cannabis affects outcome of psychotic disorders.”

The group searched relevant databases and compiled a list of more than 15,000 relevant references. A total of 13 longitudinal studies were included in the quality assessment.

The authors concluded that, despite prevailing clinical opinion, it remained “unclear” whether cannabis led to worse outcomes for people with psychosis, “or whether this impression is confounded by other factors. Specifically, the review authors noted that “few studies adjusted for baseline illness severity, and most made no adjustment for alcohol, or other potentially important confounders. Adjusting for even a few confounders often resulted in substantial attenuation of results.”

In the end, “confidence that most associations were specifically due to cannabis is low.”

Graphics Credit: COSMOS

addiction drugs

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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