The Cocktail: Fenfluramine/Phentermine
In the 1990s, a diet pill debacle stunned the United States. Fenfluramine/Phentermine, a combination of two potent uppers which had occasionally fatal side effects, scandalized the Washington bureaucracy by revealing how industry pressure could fast track a drug’s approval against the public interest. Working in combination, Fen and Phen induced the central nervous system to release elevated levels of serotonin, dopamine and norepinephrine – a pharmacological flood emulating concurrent doses of meth, cocaine and Ecstasy.
It was a hit. FDA administrators approved the drug over the objections of the agency’s own medical officer and Americans began to learn how fun weight loss can be. The party didn’t end until the FDA became flooded with reports of major, sometimes fatal, heart damage among the drug’s users. The Fen-Phen manufacturer Wyeth eventually paid more than $13 billion in legal fees and damages.
The Off Switch: Rimonabant
In 2007, the FDA — perhaps still chastened by their disastrous stumble over Fen-Phen a decade earlier — rejected the New Drug Application submitted by French pharmaceutical giant Sanofi-Aventis for their diet drug Rimonabant on the grounds that the drug manufacturer had not sufficiently proven its safety. Aventis withdrew the application, announcing that it would submit a new one shortly. The company had already received approval to sell the drug as an anti-obesity medication in the European Union and many reasonably assumed that a couple years of real-world testing across the Atlantic would prove to the FDA that the Fen-Phen debacle had made them skittish.
From a medical point of view, Aventis had good reason to believe that Rimonabant would be safer. Instead of copying the effects of street drugs like its American rival, the European drug did very much the opposite; known colloquially as “the anti-marijuana” pill, Rimonabant acts as an “inverse CB1 agonist,” meaning that it binds to the receptor commonly thought to cause marijuana intoxication but has the reverse effect of THC. Beginning with the insight that CB1 activation leads to the famous “munchies” of cannabis intoxication, Aventis researchers developed the drug in an attempt to induce the reverse effect: to turn hunger off.
This Rimonabant did very well, and other exciting possibilities had already occurred to the company chemists; on a continent more open to the idea of medical marijuana than North America, a drug which could turn off the heavy intoxication of cannabis could sell very well indeed among Europeans who needed strong therapeutic doses but also the ability to go lucidly through their daily lives. EU approval came in 2006, and by the time of Rimonabant’s U.S. rejection, the Euros had already begun to roll in.
Deaths soon followed.
Once it became widely used in the U.K., Rimonabant revealed its alarming side effects. Users began to experience severe anxiety, depression and erectile dysfunction at a rate three times higher than the general population. Some developed sudden and severe spasms. Tragically, at least two previously healthy adults on Rimonabant developed depression so severe that they took their own lives. Horrified Europeans learned the hard way that, while cannabis cannot kill, its antidote certainly can.
The Gentle Flower: Cannabis
Around the same time that Rimonabant was clearing regulatory hurdles in the EU, a team of medical researchers at the University of Florida published a small study which seemed to turn cannabis science on its head. Examining the charts of female adults who had been referred for obesity/weight management over a 12-month period, they found a clear inverse correlation between Body Mass Index (BMI, a common measure of obesity) and cannabis use; in other words, the fatter the women examined, the less likely they were to be a regular pot smoker. Though relatively small in its sample size, the study nevertheless challenged commonly held stereotypes about “lazy stoners” eating all varieties of junk food.
The next year, a team from the University of California, San Francisco went even further. Their study, which examined almost 4,000 subjects over 15 years, confirmed that many of the stereotypes of unhealthy eating are true – but that stoners are thinner anyway. The UCSF sample of regular cannabis users ate a much higher-calorie diet than nonsmokers (3,365 calories per day versus 2,746) compounded with considerably higher triglyceride (so-called “saturated fats”) intake, clearly evidencing a fattening diet. Yet, despite the fact that the heavy cannabis smokers also drank alcohol at a rate nearly three times that of nonsmokers, their BMI tended to be lower.
But the most sensational results were still to come. In 2011, a French team examined the biometrics of over 50,000 individuals, looking for correlations between cannabis use and obesity. Their results are the starkest yet: even controlling for confounding factors such as age, sex, tobacco use and pregnancy, regular cannabis users were found to be up to a third less likely to be obese than nonusers.
Taken together, the results of these studies suggest that stoners may be much thinner than the general population, despite leading otherwise unhealthy lifestyles. If this is the case – and studies like those cited seldom prove a causal relationship beyond all doubt – then a regimen of regular pot use, in lieu of alcohol and combined with a healthy diet and exercise, may be the most effective weight loss program ever devised.
And the body count is still zero.