Does Marijuana Withdrawal Matter?

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

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

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

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

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

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

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

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

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

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

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

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

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

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

A Drug For Marijuana Withdrawal?

Researchers get good results with gabapentin.

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

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

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

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

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

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

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

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

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

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

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

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.

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.

Feds Fund Study of Marijuana Withdrawal

Probing the biology of cannabis addiction.

Addiction expert Barbara Mason of the Scripps Research Institute of La Jolla, California, will oversee a four-year study of the neurobiology of marijuana dependence under a grant from the National Institute of Drug Abuse (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.

Mason, director of the Laboratory of Clinical Psychopharmacology at Scripps, told reporters in San Diego that the research, which will also be conducted at several universities, is important work: “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.” Mason has previously done work on medical therapies for alcoholism, and on the connections between alcoholism and depression.

An article by Terri Somers in the San Diego Union-Tribune quoted Dr. Mark Gold, an addiction expert from the University of Florida: “While treatments have been developed for addictions from alcohol to nicotine and narcotics, none exists for the cannabis dependent. This research will help the field define what cannabis is and is not, and how to treat it.”

Among the withdrawal symptoms common to heavy pot smokers, according to Mason, are anxiety, anger, sleep disturbances, and bad dreams. In earlier research, Mason discovered that those seeking treatment for cannabis addiction tended to cluster in two age groups—college age and mid-50s.

The research coincides with a growing belief in the psychiatric community that cannabis dependence is real and verifiable, despite years of assertions to the contrary.

There is at present a small and controversial body of clinical research, which strongly suggests the existence of a marijuana discontinuation syndrome. Dr. Gold and others believe that roughly one out of every ten pot smokers is at risk for marijuana dependence and withdrawal.

Photo credit: Kevin Fung, Scripps Research Institute

See also:
Marijuana Withdrawal

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

medical marijuana

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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