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.

Marijuana Withdrawal Rivals Nicotine

Kicking pot or cigarettes leads to anxiety, sleep problems.

A small study in the journal Alcohol and Drug Dependence likened withdrawal from cannabis to that of withdrawal from nicotine, in the case of smokers addicted to either or both substances. The study gave further support to the growing body of evidence supporting the existence of a clinically significant marijuana withdrawal syndrome in heavy marijuana smokers.

As one cigarette smoker in withdrawal famously put it, “I cannot think, cannot concentrate, cannot remember.” Now it appears that heavy marijuana smokers who go cold turkey might be susceptible to the same symptoms of withdrawal from addiction.

Dr. Ryan Vandrey, a professor of psychiatry at Johns Hopkins School of Medicine, and principle author of the study, told Amy Norton of Reuters Health that marijuana withdrawal can cause symptoms similar to nicotine withdrawal, such as anxiety, irritability, difficulty concentrating, and sleep problems. Marijuana withdrawal, which typically affects only heavy smokers, has not been well studied or characterized in the scientific community. Some marijuana advocates view the idea of marijuana withdrawal with considerable skepticism. “These new findings give some idea of its significance,” Vandrey said, and will help inform heavy pot smokers about the symptoms they may face if they abruptly stop smoking.

In the journal article, “A within-subject comparison of withdrawal symptoms during abstinence from cannabis, tobacco, and both substances,” Vandrey and his co-authors conclude: “Overall withdrawal severity associated with cannabis alone and tobacco alone was of a similar magnitude. Withdrawal during simultaneous cessation of both substances was more severe than for each substance alone, but these differences were of short duration and substantial individual differences were noted.”

The authors argue that “cannabis withdrawal is clinically important and warrants detailed description in the DSM-V and ICD-11.” The DSM-V and the ICD-11 are standardized diagnostic classification systems used in the practice of psychiatry.

Participants in the study smoked marijuana at least four times a day, and cigarette smokers consumed 20 or more cigarettes daily.

Since, as Vandrey notes, the presence of withdrawal symptoms often leads to failure when smokers are attempting to quit, it is possible that many more people are trying—and failing—to quit marijuana than researchers have previously suspected. Dr. Vandrey suggested that since difficulty sleeping is one common symptom of withdrawal, sleep medications might be indicated in the case of severe marijuana withdrawal, but cautioned that more study is needed.

Along with insomnia and anxiety, heavy marijuana smokers often report an increase in the frequency and vividness of their dreams during withdrawal as well.

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See also: Marijuana Withdrawal nicotine

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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