Back in the 1970s, animal experiments led to groundless fears that marijuana blew holes in brain tissue. The experiments organisations like NIDA now fund are more sophisticated but the controversy still rages. George Koob, an addiction researcher from The Scripps Research Institute in La Jolla, California, claims the new message from the animals is simple: The more we discover about the neurobiology of addiction the more common elements we’re seeing between THC (tetrahydrocannabinol, the main active ingredient in cannabis) and other drugs of abuse.
And for Koob, one of these newly discovered common elements is marijauna’s ability to trigger chemical changes in the brain that lead to strong withdrawal symptoms. In humans, some researchers claim to see clear evidence of insomnia, anxiety and even flu-like symptoms in heavy cannabis users who abstain. But if there’s a consensus, it’s that symptoms are mild and variable. By contrast, Koob’s rats are shivering wrecks. Does this mean marijuana is more addictive than we think? Not a bit of it, says Roger Pertwee, a university pharmacologist and president of the Cannabinoid Research Society.
That’s because those symptoms aren’t so much observed as manufactured. The animals are injected with high doses of THC, then injected with a second chemical to block cannabis receptors in the brain. Without the block, the sharp withdrawal symptoms can’t be seen because cannabis clears so slowly that even heavily doped rats are likely to experience a gentle wind down. Another debate rages over animal studies into the short-term effects of marijuana on brain chemistry. Heroin, cocaine, alcohol and nicotine all trigger a surge in the chemical dopamine in a small midbrain structure called the nucleus accumbens.
Many researchers regard this as a hallmark of an addictive substance. Last year, experiments showed that cannabis presses the same dopamine button in rats, leading to claims that the drug must be more addictive than previously thought. To critics, it is just another example of those old exaggerated fears. What nobody tells you, says John Morgan, a pharmacologist at City University of New York Medical School, is that rats don’t like cannabis. It’s easy for them to get hooked on heroin or cocaine — but not marijuana.
Nor, Morgan claims, are researchers exactly open about awkward observations, such as the fact that there are plenty of nonaddictive drugs that stimulate dopamine in the brain. It’s easy to understand why biologists want to find simple chemical traits that are shared by all addictive drugs. Unfortunately, the differences are as important as the similarities when it comes to weighing the relative risks and pleasures involved in taking drugs. And subjectively at least, the intense rush of cocaine and orgasm-like high of heroin have little in common with dope’s subtler effects.
A compound related to the active ingredient in marijuana may be accumulating in the spinal fluid of people with schizophrenia. This might explain why many sufferers smoke pot. Many researchers blame schizophrenia on an overactive dopamine system in the brain. Daniele Piomelli and colleagues at the University of California at Irvine already knew that making rats dopamine receptors hyperactive caused a surge in anandamide, a lipid that binds to the same receptors in the brain as marijuana.
Now Piomellis group has examined cerebrospinal fluid from 10 schizophrenic patients, taken for diagnostic purposes at the Medical College of Hannover in Germany. They found that fluid from schizophrenic patients had on average twice as much anandamide as fluid from people who didnt have schizophrenia (NeuroReport, vol 10, p 1665). One explanation for the higher levels in schizophrenics is that the brain is attempting to compensate for a hyperactive dopamine system. Its the brains response to bring this dopamine activity down, says Piomelli.
But the brain cannot keep the amount of anandamide high enough to lower dopamine levels, he says. This might also explain why schizophrenics often smoke marijuana. The drugs active agent, THC, and anandamide both bind to the same receptor, so patients might be treating themselves, he says. But because pot does not act selectively in the brain, Piomelli does not consider it a useful treatment for schizophrenia. I dont think the patient wants to be high, he says. I think the patient wants to feel better.
One weakness in the data so far is that five of the patients were taking medication for their symptoms and three others were using marijuana daily. The effects of these drugs on endogenous cannabinoid levels is not known. It is imperative to continue with a larger sample, says Piomelli. The researchers are now testing fluid from more patients to see if the correlation still holds true. Health officials in Geneva have suppressed the publication of a politically sensitive analysis that confirms what ageing hippies have known for decades: cannabis is safer than alcohol or tobacco.
According to a document leaked to New Scientist, the analysis concludes not only that the amount of dope smoked worldwide does less harm to public health than drink and cigarettes, but that the same is likely to hold true even if people consumed dope on the same scale as these legal substances. The comparison was due to appear in a report on the harmful effects of cannabis published last December by the WHO. But it was ditched at the last minute following a long and intense dispute between WHO officials, the cannabis experts who drafted the report and a group of external advisers.
As the WHO’s first report on cannabis for 15 years, the document had been eagerly awaited by doctors and specialists in drug abuse. The official explanation for excluding the comparison of dope with legal substances is that the reliability and public health significance of such comparisons are doubtful. However, insiders say the comparison was scientifically sound and that the WHO caved in to political pressure. It is understood that advisers from the US National Institute on Drug Abuse and the UN International Drug Control Programme warned the WHO that it would play into the hands of groups campaigning to legalise marijuana.
One member of the expert panel which drafted the report, says: In the eyes of some, any such comparison is tantamount to an argument for marijuana legalisation. Another member, Billy Martin of the Medical College of Virginia in Richmond, says that some WHO officials went nuts when they saw the draft report. The leaked version of the excluded section states that the reason for making the comparisons was not to promote one drug over another but rather to minimise the double standards that have operated in appraising the health effects of cannabis.
Nevertheless, in most of the comparisons it makes between cannabis and alcohol, the illegal drug comes out better–or at least on a par–with the legal one. The report concludes, for example, that in developed societies cannabis appears to play little role in injuries caused by violence, as does alcohol. It also says that while the evidence for fetal alcohol syndrome is good, the evidence that cannabis can harm fetal development is far from conclusive. Cannabis also fared better in five out of seven comparisons of long-term damage to health.
For example, the report says that while heavy consumption of either drug can lead to dependence, only alcohol produces a well defined withdrawal syndrome. And while heavy drinking leads to cirrhosis, severe brain injury and a much increased risk of accidents and suicide, the report concludes that there is only suggestive evidence that chronic cannabis use may produce subtle defects in cognitive functioning. Two comparisons were more equivocal. The report says that both heavy drinking and marijuana smoking can produce symptoms of psychosis in susceptible people.
And, it says, there is evidence that chronic cannabis smoking may be a contributory cause of cancers of the aerodigestive tract. HEAVYusers of marijuana who suddenly go cold turkey have aggressive impulses as powerful as those felt by Frank Spooner The reaction is far less intense than the withdrawal symptoms of alcoholics or people addicted to cocaine or heroin, and may reflect a psychological dependence on the drug, rather than a genuine physiological addiction. But it still might be enough to keep some marijuana users from kicking their habit, says Elena Kouri, a psychologist at Harvard Medical School in Boston.
Kouri and her colleagues recruited 17 volunteers who had smoked marijuana on at least 5000 occasions, and who continued to be heavy users of the drug. They also studied 20 people who either took marijuana occasionally, or who had already given it up. None of the volunteers had a history of violence or any other psychiatric disturbance. The researchers used a computer game to measure the volunteers’ aggressive behaviour during a 28-day period of abstinence from marijuana, which was monitored by daily, supervised urine tests. The volunteers sat alone at a computer screen with two buttons.
The first added money to an account in their name, but they were told that a second would subtract money from the account of their opponent, sitting at a similar screen in the next room. On the day they gave up marijuana, and one, three, seven and 28 days later, the two players were given 20 minutes to take it in turns to push one or other button, after which they could keep the money left in their account. In reality, there was no opponent. The researchers had instead arranged for the computer to provoke the volunteers by frequently subtracting money from their account.
When tested on the third and seventh days of abstinence, this ersatz nasty opponent managed to get the heavy users noticeably hot under the collar. Says Kouri: Subjects that on day zero hadn’t cared at all that they were losing points started swearing and punching the keyboard, yelling ‘I’m going to get you back! ‘ The heavy users hit the punishment button more than twice as often as the control group on days three and seven– an increase in aggression that compares roughly with that produced by a three-week course of testosterone supplements in another study by Kouri.
The increased aggression had subsided completely by the time the volunteers were tested again at the end of the abstinence period, however (Psychopharmacology, vol 143, p 302). The study is the first to measure aggression during withdrawal from a long period of heavy marijuana use. But Margaret Haney, a psychologist at Columbia University in New York, says that people who show aggressive tendencies in the laboratory do not necessarily become violent in the real world. I would hesitate to say that it would translate to physical violence, she says.