Tuesday, February 5, 2008
Marijuana Withdrawal Revisited
Is cannabis addictive?
See also Marijuana Withdrawal
Until recently, there was very little evidence in animal models for marijuana tolerance and withdrawal, the classic symptoms of addiction. For at least four decades, million of Americans have used marijuana without clear evidence of a withdrawal syndrome. Most recreational marijuana users find that too much pot in one day makes them lethargic and uncomfortable. Self-proclaimed marijuana addicts, on the other hand, report that pot energizes them, calms them down when they are nervous, or otherwise allows them to function normally. They feel lethargic and uncomfortable without it. Heavy marijuana users claim that tolerance does build. And when they withdraw from use, they report strong cravings.
While the scientific evidence weighed in against the contention that marijuana is addictive, there were a few researchers who were willing to concede the possibility. “Probably not, for most people,” a researcher at the University of Minnesota’s Chemical Dependency Program told me in the late 1990s. “But there may be some small percentage of people who are on the same wavelength with it chemically, and who end up in some way hooked to it physically. It’s a complicated molecule.”
The difference between animal models and humans may be the difference between pure THC and naturally grown marijuana. Despite the fact that rats and monkeys find whopping doses of synthesized THC aversive in the lab, psychopharmacologist Ronald Siegel, in his book Intoxication, has documented numerous instances of rodents feeding happily on wild marijuana plants in the field. There are apparently other components in the psychoactive mix that makes marijuana what it is. When the lab version of THC is hundreds of times more potent that the genuine article, it is hard to know exactly what the research is telling us.
Some of the mystery of cannabis was resolved after researchers demonstrated that marijuana definitely increased dopamine activity in the ventral tegmental area of the brain. Some of the effects of pot are produced the old-fashioned way—by means of neurotransmitter alterations along the limbic system’s reward pathway.
A report prepared for Australia’s National Task Force on Cannabis put the matter straightforwardly:
There is good experimental evidence that chronic heavy cannabis users can develop tolerance to its subjective and cardiovascular effects, and there is suggestive evidence that some users may experience a withdrawal syndrome on the abrupt cessation of cannabis use. There is clinical and epidemiological evidence that some heavy cannabis users experience problems in controlling their cannabis use, and continue to use the drug despite experiencing adverse personal consequences of use.
The U.S. government’s essentially unchanged opposition to marijuana research has meant that, until quite recently, precious few dollars were available for pot research. This official recalcitrance is one of the reasons for the belated recognition and characterization of marijuana’s distinct withdrawal syndrome.
To pluck one statistic out of many, representing estimates made in the late 1990s, more than 11 million Americans smoked marijuana regularly in the NIDA-sponsored “National Household Survey on Drug Abuse.” What NIDA has learned about cannabis addiction, according to the principal investigator of a recent NIDA study, was that “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” (This would be roughly equivalent to 14 years of daily pot smoking).
There now exists a nice body of clinical trials showing that mice and dogs show evidence of cannabis withdrawal. (For THC-addicted dogs, it is the abnormal number of wet-dog shakes that give them away.) Today, scientists have a much better picture of the jobs performed by anandamide, the body’s own form of THC. This knowledge helps explain a wide range of THC withdrawal symptoms. 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.
These functions shed light on common hallmarks of cannabis withdrawal, such as anxiety, chills, sweats, flu-like physical symptoms, and decreased appetite. At Columbia University’s National Center on Addiction and Substance Abuse, where a great deal of NIDA-funded research takes place, researchers have found that abrupt marijuana withdrawal leads to symptoms similar to depression and nicotine withdrawal.
In a 2003 research report entitled “Nefazodone Decreases Anxiety During Marijuana Withdrawal in Humans,” published in Psychopharmacology, researchers at the New York State Psychiatric Institute used Serzone (nefazodone) to decrease some symptoms of marijuana withdrawal in human subjects who had been regularly smoking six joints of pot per day. Anxiety and muscular discomfort were reduced, but Serzone had no effect on other symptoms, like irritability and sleep problems. The drug did not alter the perceived effects of marijuana intoxication (the SSRIs didn’t, either). Serzone is another antidepressant, a modest inhibitor of serotonin and norepinephrine, but its mechanism of action is ill defined. It is not in the SSRI or tricyclic families.
To date, there is no effective anti-craving medication approved for use against the marijuana withdrawal syndrome, for addiction-prone individuals unlucky enough to suffer from it.
For more, see earlier posts:
Is Marijuana Addictive?
Photo credit: 2nd International Cannabis and Mental Health Conference Programme