Marijuana apparently is a far more insidious drug than generally thought, and alters the brain chemistry of pot smokers in ways that may make them particularly vulnerable to “hard” drugs such as heroin or cocaine, two independent research groups have found. An American-Spanish team reports in today’s issue of the journal ‘Science’ that abrupt cessation of long-term marijuana use – widely regarded as a comparatively innocuous practice with a low risk of addiction – causes the same kind of cellular withdrawal reactions in lab rats as “those produced by other major drugs of abuse.”
Although they seem fairly mild to the marijuana user, those withdrawal effects can prompt changes in nerve function that “prime” the pot-smoker’s brain for greater susceptibility to opiate, cocaine or alcohol abuse, the researchers suggest.
In a second report, Italian scientists show the major active ingredient in marijuana smoke has precisely the same impact as heroin on a key brain site that influences addiction to numerous drugs.
If confirmed by further investigation, the discoveries could tip the scales in the ongoing national debate over whether marijuana is a relatively harmless recreational drug or serves as a “gateway” to use of other, more dangerous substances – a presumption supported by the fact that more than 90 percent of hard-drug users say marijuana was their first drug.
The question is urgent because marijuana is the most prevalent illegal drug in America, with about 10 million occasional or frequent users.
Nearly 36% of U.S. high school seniors smoke or have smoked it, according to the latest federal survey. About 3 million children aged 12 to 17 use it, the Department of Health and Human Services has determined, and use in that age group has nearly doubled since 1990.
Approximately 100,000 Americans a year seek treatment for marijuana dependence.
Neither report immediately alters marijuana’s (arguable) reputation as one of the less hazardous of routinely abused substances. But taken together, the new findings not only suggest marijuana is capable of “causing physical dependence,” said Alan I. Leshner, director of the National Institute on Drug Abuse, but seem to confirm the growing suspicions of experts about the nature of all habit-forming drugs.
“More and more over the course of the last few years,” he said, “we have come to understand that there is a common set of characteristics of all abusable substances.”
On the face of it, that may seem incomprehensible. After all, cocaine, heroin, alcohol and THC (the principal mind-altering component of marijuana) affect completely different kinds of messenger chemicals, known as neurotransmitters, in different parts of the brain and body.
Moreover, cocaine is a stimulant, whereas alcohol and opiates such as heroin are powerful depressants. Superficially, they appear to have almost nothing in common.
Yet they do. For one thing, withdrawal from any of those drugs causes the same kind of distress response among nerve cells in a brain structure called the amygdala, part of a central-brain system involved in controlling emotions. When a habitual user suddenly quits, neurons in the amygdala start pumping out a substance called corticotrophin releasing factor (CRF), which is part of the brain’s response to stress and the panicky tension of withdrawal.
That effect has been observed repeatedly in the case of hard drugs, but has never been seen convincingly for marijuana because THC is eliminated very slowly from the body. When chronic pot smokers suddenly stop use of the substance, they frequently report restlessness, sleep disturbance and high anxiety. But the effects are muted because THC persists in fatty tissues; 30 hours after smoking pot, about half the THC is still in circulation, even though the user has quit feeling high.
NIDA-funded researchers set out to see what would happen if they somehow could bring marijuana’s effects to a screeching neurological halt. They gave rats a daily dose of a THC-like substance for two weeks and then injected them with a newly concocted compound that blocks the THC receptors, When the scientists looked at he rats’ brains, they found exactly the same kind of increased CRF production seen in opium, cocaine or alcohol withdrawal. Activating the CRF system, many experts believe, can promote addiction of all kinds by making the person more sensitive to unpleasant sensations and thereby prone to take another drug dose. Thus, repeated marijuana use, the researchers write, may leave the brain “primed” for “future vulnerability to drug dependence.” A second surprising and recently uncovered similarity among popularly abused drugs is that all of them appear to cause a build-up of a potent messenger chemical called dopamine in another central-brain section called the nucleus accumbens. Dopamine is a crucial constituent of the neural pleasure response, or “high,” much of which is triggered in the nucleus accumbens and telegraphed to other brain areas. Morphine, cocaine, amphetamines and nicotine all produce drastically increased dopamine transmission in the nucleus accumbens, and scientists from the University of Cagliari in Italy wanted to find out if THC and heroin would do the same. They gave rats intravenous doses of both drugs, and found that both brought on a dopamine spike. In addition, they gave other rats a drug that completely blocks the action of heroin in the brain. That drug, they found, also prevented THC activity, indicating that that heroin and marijuana effect some highly similar, if not identical, changes in brain chemistry. “Although our results do not provide direct evidence for a causal relation between (marijuana) and heroin use,” the scientists write, “they are nonetheless consistent with this possibility.”