IS MARIJUANA ADDICTIVE?

There's a lot of science on the books on the question of marijuana's
addictive properties, but is the issue too politicized to get any
clear answers?

Is marijuana addictive?

The National Institute on Drug Abuse (NIDA) says it is. According to
its "Marijuana Abuse" research report, "Long-term marijuana use can
lead to addiction; that is, people have difficulty controlling their
drug use and cannot stop even though it interferes with many aspects
of their lives."

The Office of National Drug Control Policy's abovetheinfluence.com Web
site is blunter. "Marijuana is addictive, with more teens in treatment
with a primary diagnosis of marijuana dependence than for all other
illicit drugs combined," it declares.

Sentiment among marijuana users and advocates is the exact opposite.
While a minority of pot-smokers get high so frequently it impairs
their functioning, the vast majority insist they can do it
occasionally or regularly without problems.

The word "addiction" conjures up the stereotype of a heroin junkie,
willing to lie, manipulate, steal, and perform cut-rate oral sex in
order to avoid suffering the withdrawal--nausea, diarrhea and flu-like
distress--that comes after they go without the drug for several hours.
Cocaine, however, does not produce a similar physical withdrawal. So
over the last generation, the concept has evolved to a more complex,
subjective model.

NIDA now calls addiction "a complex illness characterized by intense
and, at times, uncontrollable drug craving, along with compulsive drug
seeking and use that persist even in the face of devastating
consequences." The DSM-IV, the fourth edition of the Diagnostic and
Statistical Manual of Mental Disorders, lists the criteria for drug
"dependence" as tolerance, withdrawal, continuing to use despite
negative psychological or physical consequences, using more than you
want to, unsuccessful attempts to cut down or quit, excessive time
spent procuring the drug, and withdrawal from social, work or family
obligations.

Some marijuana users reach that point. "Marijuana controls our lives!"
the 12-step recovery group Marijuana Anonymous exclaims on its Web
site. "Our lives, our thinking, and our desires center around
marijuana--scoring it, dealing it, and finding ways to stay high."

The vast majority don't reach that point. Among the commonly used
drugs, pot is the least likely to cause dependence. The estimate most
often cited, based on a NIDA-supported survey from the early 1990s, is
that 9 percent of people who use marijuana will develop dependence at
some point in their lives, compared with 15 percent for alcohol, 17
percent for cocaine, 23 percent for heroin, and 32 percent for tobacco.

Mitch Earleywine, author of Understanding Marijuana: A New Look at the
Scientific Evidence and a psychology professor at the University at
Albany in New York, disputes that 9 percent figure. If you focus on
genuine problems, "instead of some manufactured diagnosis," he says,
maybe 4 to 8 percent of regular marijuana users have problems.

The two main arguments that cannabis is addictive are the number of
people admitted to drug-treatment programs primarily for marijuana use
and research indicating that chronic use may cause a withdrawal syndrome.

The proportion of people admitted to rehab primarily for marijuana use
increased significantly from 1999 to 2009, from 13.5 percent of
admissions to 18 percent of the nearly 2 million tracked by federal
Substance Abuse and Mental Health Services Administration in its
Treatment Episode Data Set. More than half of teenagers in rehab were
there for pot.

However, according to SAMHSA figures from 2009, 56 percent of the more
than 350,000 people admitted to drug treatment for marijuana were
referred by the criminal-justice system, such as after an arrest or
probation violation. Only 15 percent were "self-referred," seeking
rehab voluntarily. For the 282,000 heroin admissions, the proportions
were exactly the opposite: 55 percent came in on their own, and only
15 percent were referred by legal authorities. For crack, 36 percent
of the about 130,000 admissions were self-referred, and 29 percent
sent over by the criminal-justice system.

The National Organization for the Reform of Marijuana Laws notes that
the increase in pot-rehab admissions parallels "the proportional
increase in marijuana arrests reported over the same period."

Teenagers are less likely to come in without pressure, counters Alan
Budney, a professor of psychiatry at the University of Arkansas for
Medical Sciences Center for Addiction Research. In the adolescent
clinic he runs, "only about 5 percent of kids say 'I need help.'"

Evidence of Withdrawal

There is some evidence emerging that marijuana causes withdrawal. Over
the last 15 years, several experiments have demonstrated withdrawal
symptoms in mice, rats and monkeys. In a 1998 study at Virginia
Commonwealth University, mice were dosed with massive amounts of THC,
from 10 to 30 milligrams per kilogram of body weight, twice a day for
a week, and then injected with rimonabant, a "cannabinoid antagonist"
that blocks the brain's CB1 receptors for both endogenous cannabinoids
and THC. That "promptly precipitated a profound withdrawal syndrome."

The mice got "very dramatic withdrawal" symptoms such as "wet-dog
shakes," says Dale Deutsch, a biochemistry professor at Stony Brook
University and former head of the International Cannabinoid Research
Society. A 2010 study from the University of Texas Health Science
Center found that rhesus monkeys given 1 mg/kg of THC twice a day
developed head shaking and sleep disturbances after being given
rimonabant, and that those symptoms eased after the monkeys were again
given THC.

Earleywine dismisses those studies as "artificial." The rimonabant, he
notes, "tosses the THC off every cell in their body at once. That's so
unlike what happens in humans." Even so, he adds, the shakiness
described as "withdrawal" in mice lasted only 15 minutes.

"They never were able to show there was any clear-cut withdrawal until
rimonabant," says Deutsch. "In real life, however, the THC hangs
around a long time, and you do not get precipitated withdrawal unless
you give an antagonist."

THC has a much longer half-life than other drugs. Cocaine is half gone
from the body within 90 minutes. Heroin, even after being metabolized
to morphine, takes two to seven hours. But as THC is absorbed by the
body's fatty tissues and membranes, its half-life is at least three to
four days, and has been estimated at 12 days in chronic marijuana
users. (That is also why drug tests are more likely to detect
marijuana than cocaine or heroin.)

The mice also got doses of THC far above what humans would normally
consume. For a 154-pound human, 10 mg/kg twice a day would be like
smoking a half-ounce of 10 percent-THC pot in one day--with none of the
THC going up in smoke. The minimum effective dose of THC in humans,
notes Deutsch, is 10 micrograms per kilo of body weight.

The reason for such large doses, says Aron Lichtman, a pharmacology
and toxicology professor at Virginia Commonwealth University who
coauthored a 2002 study on cannabis withdrawal in rodents, is that
rats and mice metabolize drugs very quickly. They have "very efficient
livers," he says.

It's normal to give rodents 10 times the equivalent human dose in drug
experiments, he explains; it's also done in studies of cocaine and
morphine. Humans in marijuana studies also get very high doses, he
adds.

Rimonabant is used, he explains, because "spontaneous
withdrawal"--symptoms that develop merely from stopping the drug--is
hard to reproduce in rodents. It has been observed in monkeys, he
says. One study found them more active at night 24-48 hours after
cessation of THC.

However, Deutsch says, rimonabant may cause problems on its own,
because it interferes with the body's endogenous cannabinoid system. A
French drug company sold it as an appetite suppressant, but it was
taken off the European market in 2008 because it increased the risk of
depression. The U.S. Food and Drug Administration rejected it for
similar reasons in 2007. In the 2010 University of Texas study, the
control group of monkeys that were given rimonabant but no THC also
developed head shaking and tachycardia.

Symptoms of Withdrawal

The evidence for cannabis withdrawal in humans is based on inpatient
studies involving abstinence after sustained consumption of oral THC
or smoked cannabis, and also on symptoms either described in
interviews or checked on lists by people in rehab and in studies of
outpatients trying to quit.

The main complaints, says Alan Budney, are irritability,
sleeplessness, anger, restlessness, and "not feeling right." They also
include appetite loss and, less frequently, depression and nausea.
They peak after two or three days of abstinence and last a week or
two, he wrote in 2008.

"There's no doubt that it exists. We see it all the time in clinics,"
he says. When he first published his studies, he says, he got phone
calls from Marijuana Anonymous thanking him for confirming what its
participants had been talking about in meetings.

The concept is "still somewhat controversial," says Lichtman.
Earleywine believes it is "very misleading" to use the word
withdrawal. "There's obviously some mild discomfort in humans who quit
suddenly," he says, "but the connotations of the word 'withdrawal'
make people think of heroin." He also finds it absurd that loss of
appetite is considered a symptom of marijuana withdrawal, given that
"it's a drug so notorious for enhancing appetite that it's got its own
expression--the munchies." The DSM-IV did not include cannabis
withdrawal, on the grounds that its symptoms' "clinical significance
is uncertain." Budney is trying to get it listed in the forthcoming
DSM-V.

"We think it's important enough," he says. He adds that he's not on a
crusade against marijuana: "I'm out there helping people who want to
quit."

Whatever cannabis withdrawal is, it's definitely much milder than
detoxing from heroin or alcohol. Stopping drinking can cause fatal
seizures in severe alcoholics, notes Carl Hart, a neuroscientist at
Columbia University College of Physicians and Surgeons. He calls
cannabis withdrawal "unpleasant but not threatening." "It's certainly
not like heroin withdrawal," says Budney. But he adds that the "milder
symptoms are what make people go back and smoke."

Those symptoms are likely confined to a minority of potheads. Hart
says they appear in a "select group of heavy, heavy users"; some, but
not all, people who smoke several joints a day will have sleep
disturbances and become irritable when they quit. Budney estimates
that half of heavy users and "not a high percentage" of moderate users
will suffer withdrawal.

Dr. Jeff Hergenretter, a Sebastopol, California, physician who has
been seeing mainly medical-marijuana patients for the past 12 years,
says the number is insignificant. Less than 1 percent of his 2,000
patients, he says have described any withdrawal symptoms, "and it's
short-lived, mild, lasting a day or two." The vast majority have "no
withdrawal symptoms whatsoever. No discomfort, no dysphoria, no nothing."

Marijuana withdrawal is most comparable to quitting cigarettes, says
Budney. In a study he published in 2008, tobacco smokers and daily
pot-smokers who were trying to quit reported equal levels of
discomfort in telephone interviews. However, 44 percent of the
cigarette-smokers were using nicotine-replacement therapies such as
patches.

That "definitely would warp results," he agrees, but "we just had to
take who we had." Nevertheless, he says, the people using nicotine
replacement also reported being irritable, and an "accumulation across
these studies" confirms his theory.

"Most people think it's akin to coffee craving. I know that's true in
my case," says Fred Gardner, editor of O'Shaughnessy's, a
California-based magazine devoted to medical-marijuana research.

"Caffeine withdrawal may be in the DSM this time," says Budney. While
coffee can improve people's work functioning, he explains, those who
stop drinking it can suffer acute headaches.

"I don't get withdrawal. I just miss smoking it," says one veteran
pothead, an artist who can't afford to buy as much since he and his
wife lost their day jobs in the Great Recession. But another longtime
toker, a college professor, says, "when I don't smoke for a couple
days, I get headaches."

Addiction Neuroscience

Scientists have not yet been able to explain why some people will get
intoxicated compulsively and destructively, while others can take the
same drug and not develop such problems. Starting use at a younger age
and having had a traumatic childhood definitely increase the risks,
but there are large and poorly understood variations in individuals'
personalities and neurochemistry. For similar reasons, it is hard to
predict how depressed people will respond to various medications.
"It's just like how people respond to meds. Not everything is
pharmacological," says Budney. "People are vulnerable. Some are more
vulnerable than others."

"That you have some sort of withdrawal really isn't important," Carl
Hart avers. If treating withdrawal was all that was needed to get
people to stop using a drug, he explains, it would be easy. The issue
is more about how people use the drug than about the pharmacology of
it.

"Whether or not our addiction is psychological, physical, or both,
matters little," Marijuana Anonymous says. "When it comes to the use
of marijuana, we have lost the power of choice."

The neurological basis for cannabis withdrawal is "still an open
question," says Lichtman. A Spanish researcher recently found that THC
inhibits a brain-messenger chemical called cyclic AMP, and that
quantities of cyclic AMP "overshoot" in the cerebellum during
withdrawal. However, he cautions, this is just a correlation, not
clear proof of changes in the brain.

Only a small percentage of marijuana users become dependent, he says,
but "given the huge numbers of people smoking marijuana, even if
[dependence] is a low amount, that's still a huge number of people."

Marijuana "doesn't meet what I think are stringent definitions of
addiction. Habit-forming it is, addicting it isn't," Dr. Hergenretter
responds. "I have one patient out of 2,000 who describes himself as
addicted to cannabis. He says that every time he gets some, he smokes
it all and wants more. He's really an exception. He's one of the rare
cases who describes a dysphoria the next day if he doesn't smoke."

The 9-percent dependence figure "doesn't meet reality in any real
way," Hergenretter continues. While users develop tolerance, he
explains, it's very common for them never to increase how much or how
often they smoke, and most are not "socially damaged by need for
marijuana," not compelled to use it to the point of "stealing their
neighbors' TV."

With more than 800,000 people a year arrested for marijuana, the
definition of "dependence" has been politicized, Mitch Earleywine
says. "The distinction between 'psychological' and 'physical'
addiction is completely invented," he argues. "When later editions of
the DSM came out, psychological was added primarily because cannabis
wasn't creating withdrawal symptoms, and prohibitionists wanted there
to still be some sort of cannabis dependence. So dependence suddenly
became two types: 'with physical' and 'without physical features.'
Essentially, if you had enough problems but didn't show tolerance or
withdrawal, you could still get a dependence diagnosis."

One of the main criteria for defining problematic drug use is
continuing to get high even in the face of negative consequences. But
if getting arrested is one of those consequences, responds Fred
Gardner, "that's a function of prohibition."

Many marijuana users see risking arrest to grow, buy and smoke the
herb as defying an unjust law, not a symptom of addiction.