Source: Reason Magazine Contact: March 1, 1998 Website: http://www.reason.com/ Author: John P. Morgan John P. Morgan, a physician and professor of pharmacology at the City University of New York Medical School, is co-author of Marijuana Myths, Marijuana Facts (Lindesmith Center). DRUG TRIAL: MEDICALIZATION AND SCIENTISM (5 of 8) Medicalization - the idea that drug consumption can be understood by a scientific assessment of what drugs do in the body and brain - is not new. Many physicians in the late 19th century tried to explain heroin or morphine addiction as a kind of allergic reaction: The repeated injection of opiates permanently changed the user's physiology, creating an illness requiring lifelong use of the drug. Today, medicalization relies on apparently scientific explanations of the neurobiological mechanisms underlying addiction. Research in this area is increasingly complex, if not abstruse, and journalists look to the investigators themselves to explain how important and revealing it is. These scientists take a pharmacocentric approach, focusing on the drug as the cause of behavior and ignoring other factors. Their reports are scientistic, using the neutral language of neurobiology to disguise value judgments. Investigators usually assert that results from animal or cell-culture experiments are clearly relevant to humans. Indeed, they often claim that a given study "proves" the existence of a human drug reaction that cannot be found among humans. Two highly publicized studies reported in the June 27, 1997, issue of Science illustrate these tendencies. In one, Fernando Rodriguez de Fonseca and other investigators at the Scripps Research Institute in La Jolla gave rats daily injections of a synthetic drug resembling delta-9 tetrahydrocannabinol (THC), the main active ingredient in marijuana, for two weeks. Then they gave the rats a cannabinoid antagonist, which stripped the THC-like drug from its receptor sites. This provoked a withdrawal syndrome lasting an hour or so, featuring tremors, hyperactivity, and defensive posturing. The researchers also measured increases in brain concentrations of corticotropin-releasing factor (CRF), a neural hormone. Such increases have been seen in rodents undergoing alcohol and heroin withdrawal. The study and an accompanying editorial said these findings confirmed cannabinoid withdrawal in humans and provided evidence that increases in CRF create anxiety that drives marijuana users to ingest other drugs. De Fonseca et al. claimed their study therefore offered support for the "gateway" theory, which says smoking marijuana leads to the use of cocaine and heroin. In the second study, Gianluigi Tanda and other researchers at the University of Cagliari in Italy measured the release of dopamine in the mesolimbic area of the rodent brain following injection of THC, a THC-like synthetic, and heroin. Neurobiologists have long wondered if cannabinoids raise extracellular dopamine in this brain area because such increases are triggered by many drugs that humans use for pleasure, including heroin, alcohol, amphetamine, nicotine, and cocaine. Prior to the Tanda study, evidence of dopamine release caused by injection of cannabinoids was equivocal. In their report, Tanda and his colleagues unhesitatingly compared marijuana to heroin and, like de Fonseca et al., invoked their rodent findings as evidence for the much-discussed gateway theory. They speculated that marijuana use, by increasing dopamine, "primes" the brain, so the dissatisfied cannabis smoker will be drawn to heroin for the familiar dopamine rush. Both studies were widely covered in American newspapers, framed in just the way suggested by the researchers. Their extrapolations to humans were reported without qualification, and their results were described as "new evidence" of marijuana addiction and a gateway effect. This unscientific interpretation ignored the findings of prior research involving both animals and humans. Rodents and primates will not self-administer THC or other cannabinoids even when they have been primed with repeated injections and abrupt withdrawal. Simply put, these animals do not like pot; they find small doses unappealing and large doses aversive. Hence the de Fonseca study, in which the researchers went to great lengths to precipitate a short-lived cannabinoid withdrawal reaction in rats, has no obvious relevance to animal behavior, let alone human use, which typically involves smoking small amounts of cannabis episodically, with THC declining slowly after each session. De Fonseca et al.'s most egregious extrapolation was their speculation that cannabis smokers move to other drugs because of the "anxiety" seen in withdrawal. It is difficult to show any marijuana withdrawal phenomenon in humans, and I know of no study that links cessation of cannabis use with the use of other drugs. Yet somehow the release of a neural hormone in rats signaled to the researchers that human cannabis users suffer abstinence anxiety that they try to alleviate with cocaine or heroin. Similarly, it's hard to know what to make of the dopamine increases found in the Tanda study, since rats do not actually like cannabinoids. Earlier research in this area was based on the theory that reinforcing drugs raise dopamine levels. Now we have an experiment linking increased extracellular dopamine with a compound that is not reinforcing in rodents and has not been shown to be an important drug of dependence in humans. There are many drugs that increase extracellular dopamine which humans do not find attractive, including levodopa, tricyclic antidepressants (Elavil, Tofranil), and anticholinergics (atropine, Artane). These attempts to scare people about marijuana through animal studies, because actual human experience with the drug is not alarming enough, suggest the pitfalls of the biological reductionism on which medicalization depends. Where medicalization is the practice, scientism is the theory. [continues]