POT'S TAB IN THE WAR ON DRUGS

The Arkansas Times, September 16, 1993

REEFER MADNESS

While courts send users to prison, scientists at NCTR find little to support dangers of pot.

The investment:

* Federal matching funds for the "war on drugs" in Arkansas totaled $4.6 million in 1992.

* State and local agencies kicked in another $1.8 million.

* The Arkansas National Guard received $1.3 million to assist in marijuana eradication.

* An unknown additional amount of money was generated for drug investigations by the sale of confiscated property.

* No figures are available for the cost of prosecuting drug cases and incarcerating offenders.

The return:

* 42 percent of all arrests for the sale and manufacture of drugs in 1992 were for selling or growing marijuana.

* And 62 percent of all arrests for possession of drugs were for possession of marijuana.

By Mara Leveritt

The monkeys smoked a joint a day. Actually, they didn't recline in their cages, puffing a hand-rolled reefer. This being a scientific experiment, funded by the powerful National Institute on Drug Abuse, the process was more carefully controlled. The monkeys were fitted with masks through which marijuana smoke, machine-puffed in carefully measured doses, was passed into their nostrils.

The experiment, performed at the National Center for Toxicological Research near Pine Bluff, was designed to test whether chronic marijuana use caused brain damage. It lasted for several years, with the most intensive phase, during which monkeys were exposed to heavy doses of marijuana smoke, occurring from 1984 to 1985.

Reports on the study's findings continue to be published in pharmacology and toxicology journals. But beyond those tight scientific circles, the results of the NCTR experiment, the most extensive of its kind yet conducted, have gone almost entirely unnoticed.

That's not surprising, perhaps. In a world where the political majority has shown little tolerance for marijuana, the test results are explosive.

The experiment discovered no adverse impact from marijuana on monkeys' general health, no sign that heavy exposure to marijuana smoke caused lung cancer, and, with one exception, no long-term effects on the animals' behavior from exposure to marijuana.

Before the NCTR study, the largest experiment examining the effects of marijuana on primates was one conducted at the Stanford Research Institute. That experiment, focusing on the brain's electrical activity under the influence of marijuana, involved 16 monkeys.

By contrast, the experiment at NCTR used 62 monkeys, all rhesus males. In 1983, the animals were all approximately two to three years old, the monkey equivalent of teen-agers.

For one year before the start of the experiment, the monkeys were trained to play "games" designed to test their perception of the passage of time and their ability to discern left from right. Only after they were proficient did the exposure to marijuana begin.

Toxicologists divided the monkeys into four groups. Every day for a year, 16 monkeys each received what Dr. Merle Paule, head of NCTR's Behavioral Toxicology Laboratory and Primate Research Facility, called "a pretty heavy exposure" to marijuana, the human equivalent, Paule said, of "four or five joints a day."

Another group of 16 smoked the same amount of marijuana, but only two days per week. Staffers called them the "weekend smokers."

A third group was administered smoke from cigarettes identical to the others, except that the psychoactive component of THC had been removed. And a fourth group received no smoke exposure at all.

The monkeys smoked for a year, then they were monitored and tested for another year.

Dr. William Slikker, acting director of NCTR's Division of Neurotoxicology, explained that the study generated so much data, it has taken time to compile it and the results have been released gradually, in several reports since the experiment was ended.

In 1991, the journal Fundamental and Applied Toxicology published a report on the effects of marijuana on the monkeys' general health. Slikker was the lead writer, with Paule (pronounced Paul) and other NCTR researchers listed as collaborators.

That report concluded, "The general health of the monkeys was not compromised by a year of marijuana smoke exposure as indicated by weight gain, carboxyhemoglobin and clinical chemistry/hematology values.

"Most clinical parameters ... did not show any treatment-related changes, and those few that did were of small magnitude, transient in nature, and were not different at the end of the five-month postdosing period."

Last week, in his office at NCTR, Paule explained the health study's results in more casual terms. "There's just nothing there," he said. "They were all fine."

Last year, the journal Toxicology Letters published a report by another group of NCTR researchers on the effects of marijuana on the lungs of the monkeys who smoked. Seven months after the last exposure to marijuana smoke, some of the monkeys were killed and their bodies autopsied. Scientists examined the lungs for signs of disturbances called "carcinogen-DNA adducts," considered to be one of the early indications of cancer.

The writers of that study reported that although their findings were not conclusive, they were "at variance with earlier work suggesting that fractions of marijuana smoke are highly genotoxic."

The seven authors noted that, "It has been suggested that marijuana smoking is a proximal cause of respiratory cancer. However, these intimations have not been borne out by epidemiological investigations, which is surprising considering the widespread use of marijuana."

Moreover, the journal article noted: "The data presented here suggest that seven months after the last smoke exposure, there is not evidence of increased marijuana smoke-induced carcinogen-DNA adducts in the lungs of exposed monkeys."

Paule's informal interpretation: "If it's not there, it's probably not too terrible."

(The researchers discount the claim that as marijuana has become increasingly potent, due to refined horticultural techniques, it has also become more dangerous. Other studies, they say, have demonstrated that smokers inhale only to the point of inebriation, so that persons smoking stronger marijuana smoke considerably less of it.)

Late last year, Paule himself was the lead author of a report published in The Journal of Pharmacology and Experimental Therapeutics. It dealt with marijuana's effect on behavior.

This report's findings were more complex.

Before the monkeys were started on their year-long smoke exposure, Slikker, Paule and other scientists, conducted a short-term study to determine the immediate effect of THC on the animals; in other words, how they reacted when they were "high."

They found two areas of apparent impact. One was the monkey's short-term memory. "That's a function that's very sensitive," Paule explained, "but only on an acute basis. If you test them the next day, you see no residual effect on those behaviors."

The monkeys sense of time also appeared disrupted. Monkeys, it turns out, are as good as humans at estimating the passage of time. Members of both species to equally well at a test that requires them, for instance, to press down on a lever for more than 10 seconds but not longer than 14 seconds.

Marijuana has been shown to affect human's ability to perform the test at normal levels, and the monkeys were no different. "That time-estimation behavior is exquisitely sensitive to marijuana," Paule said, "even at very low doses."

The NCTR study corroborated human studies showing that time seems to stretch out for many subjects under the influence of marijuana. In the monkeys' response to the time-perception test, Paule explained, "what they said was that eight seconds feels like ten."

That phenomenon too, however, quickly dissipated. Testing the next day showed the monkeys' time perception restored to its normal acuity.

The main thrust of the study, however, concerned the long-term effects of exposure to marijuana. To study that, the animals were tested for cognitive function and motivation 23 hours after each marijuana exposure.

The cognitive test involved four lights and two levers. The monkeys were taught that when they saw a red or a yellow light, they were to hit a lever on their left in order to receive a food pellet. If a blue or a green light came on, they would get the pellet by hitting a lever on their right.

The researchers wanted to see if the animals scored any differently 23 hours after exposure to marijuana than they had before receiving the drug. "On that test," Paule said, "their performance was unaffected."

The test of motivation, however, showed a definite pattern of change. This test required the monkeys to put forth an increasing amount of effort to get food. Since a decrease in motivation or "work ethic" has been described as one of the effects of smoking marijuana, the researchers wanted to see "how much effort the monkeys were willing to put out," as compared to the nonsmoking control group.

Their paychecks were banana-flavored food pellets. For the first pellet, the monkeys had only to depress a lever once. They had to hit it twice to get the second pellet. And for a third pellet, they had to pump the lever three times.

Here, the group exposed to THC showed a clear unwillingness to get worked up about work. Paule pointed out that during the year the test was being conducted, the monkeys were passing from adolescence into adulthood, a time for them, as for humans, he said, when "the work ethic normally goes way up."

But that improvement didn't show up in the marijuana-smokers. While the nonsmoking monkeys showed a willingness to work harder and harder as the year progressed, the marijuana groups stayed at adolescent levels.

"Our interpretation of this is that marijuana smoking in monkeys does produce something akin to an amotivational syndrome," Paule said. He added, however, that the phenomenon may have occurred precisely because the monkeys were at the critical and deliberately chosen stage of adolescence when the NCTR test was conducted.

Because marijuana use is high among teenagers, depressed motivation at that stage in life can have serious effects. But marijuana may not have the same effect on adults.

"We did a search of the literature," Paule said, "and we found that those studies that tried to find amotivational syndrome in adults could not find one. It only appears in adolescence. Chances are, if we'd done these studies in adults, we wouldn't have seen this effect. And the good news is that, even among adolescents, when the exposure to marijuana was stopped, their motivation jumped right back up to normal levels."

"It took two to three months for them to recover to full values, but they did recover and they recovered fully."

Paule noted two other findings related to the motivational test. One was that the willingness to work appeared to be equally affected in both the daily and weekend smokers. "That totally surprised us," he said.

Another finding worthy of note was that, as in most areas of life, one monkey proved to be an exception. As Paule put it, he seemed to go "blooey" under the influence of marijuana.

"Unlike the others, we found that this one particular animal was severely disrupted by chronic marijuana exposure on the discrimination task. And he never recovered full from the amotivational syndrome. We have no understanding of why. Everything else about him tested normal."

That one monkey represents a warning. As Paule cautioned, "There appears to be tremendous individual variation in susceptibility to marijuana."

Also of interest in the NCTR study, in light of U.S. criminal sanctions against marijuana, is the researchers' observation that the animals exposed to marijuana never posed a threat to their handlers.

"I've never seen anything that suggests marijuana is responsible for an increase in any violent behavior," Paule said, adding, "I would say that the perceived risk to marijuana is probably overstated."

That's the scientist speaking. Here's the father. Asked what he would tell his 9-year-old son about the risks of smoking marijuana, this was Paule's answer: "I'd tell him he probably shouldn't smoke dope before he becomes an adult."

POT RESEARCH LID ABOUT TO BLOW OPEN

Dr. Don McMillan, chairman of the Department of Pharmacology at the University of Arkansas at Little Rock, is also the school's Wilbur D. Mills professor of Alcoholism and Drug Abuse Prevention. He led a major study into human tolerance of marijuana in the early part of his career, and more recently served as an advisor to the researchers at NCTR in planning of their study of marijuana's effects on monkeys.

After years during which he said marijuana research was "stalled," McMillan is once again excited about developments in the field.

"It looks like the whole lid on marijuana research is about to blow wide open," he said in a recent interview. "I think we're going to know a tremendous amount more about the mechanism of action and how it works on the brain in the next two years."

As marijuana is studied further, its effects, especially relative to other, legal drugs, will also become better understood. For example, marijuana is ranked with heroin and LSD as a Schedule I drug. The federal government rates its potential for abuse higher than the risk of abusing cocaine, morphine, PCP, or methadone.

Asked about that, McMillan said, "The thing you have to remember is that that schedule is a legal classification, not a medical one."

He said the medical understanding of marijuana is that it poses a lower risk to society and individual health than that of two legal drugs -- alcohol and tobacco.

"Marijuana is probably less harmful than either of those -- but of course, there's still a lot we don't know about it."

The Arkansas Times, September 16, 1993, pp. 11-12

From The Iowa NORML News Letter, Fall 1994, pages 2-4 (reprinted with permission from The Arkansas Times).