The Villain Leshner

I don't know which chemicals are released in which parts of the brain, but there's a pleasurable rush when you find yourself in agreement with someone who has been observing the same scene from a completely different angle. Civilians who opposed US intervention in Vietnam in the 1960s will remember how affirming it was to see Master Sergeant Don Duncan, the most highly decorated enlisted man in the US Army, saying “I quit!” on the cover of Ramparts. Dr. Carl Hart quit the War on Drugs, he says in Drug Use for Grown-ups, not because it's a failure but because it has succeeded in achieving its real, unrighteous goals.

Hart originally enlisted, he recounts, because ”It was clear to me that the poverty and crime in the resource-poor community from which I came was a direct result of recreational drug use and addiction. I reasoned that if I could stop people from taking drugs, especially by fixing their broken brains, I could fix the poverty and crime in my community.” Over the course of a decade, his own research and a critical reading of colleagues' papers led him to question whether recreational drug use inevitably causes brain damage.

In a chapter called “Drug Addiction is not a Brain Disease,” Hart examines some concepts he had accepted en route to a PhD in neuroscience and a professorship at Columbia. For example, “The overly simplistic idea... that when a person experiences pleasure, including from recreational drugs, they do so because the dopamine neurons in the nucleus accumbens have become active. Methamphetamine, for example, causes a release of dopamine in the brain region and this increased release is correlated with feelings of pleasure. This basic but highly incomplete knowledge essentially led me, and many, many others, to conclude that there must exist discernible and meaningful brain differences, especially in these dopamine-rich areas, between those who use drugs and those who do not. These differences, I thought, must be the cause of addiction and other problems related to drug use.

“In 1997 this position was argued eloquently by Dr. Alan Leshner, then director of NIDA, when he published in the journal Science an influential editorial entitled 'Addiction is a Brain Disease, and it Matters.' He explained, “That addiction is tied to changes in brain structure and function is what makes it, fundamentally, a brain disease. “Alan's paper solidified my loyalty to the 'drugs are bad for your brain' camp. I was a true believer, and his editorial was my holy writ.”

In May 1998 I heard Leshner push this message vigorously in a talk at UCSF. The occasion was the launching of a “Center for the Neurobiology of Addiction” —a fund-raising device poetically described by the university's press release as “a building without walls.” Cole Hall was packed with motivated neuroscientists, postdocs and graduate students. (Rich men named Wheeler and Samuelson had pledged millions to underwrite addiction-related research at UCSF.)

The NIDA chief was trim, of average height and looked a lot like the proprietor of the shoe store my mother took us to in Brooklyn a long time ago; but unlike weary Mr. Kaplan, Leshner had a wolfish gleam in his eye and his clothes were expensive. He used pomade and light pancake make-up, a first for people giving talks at UCSF. The acting chancellor introduced him, describing a steady ascent from the Psychology Department at Bucknell to the National Science Foundation, the National Institute for Mental Health and then the top job at NIDA. 

Leshner said with a smile, “I grew up in the mental health business, as you heard.” He had commandeered slides from some NIDA addiction experts, he said, smiling, because “After all, I’m the director of the Institute.” Did he think he was being down-to-earth? He seemed just plain crass. He plugged a book recently published by NIDA, “Prevent Drug Use Among Children & Adolescents: A Research-based Guide.” Showing a slide of the cover, he said with a modest smile, “It’s becoming a bible.” 

Leshner wanted the assembled researchers to devote themselves to identifying the types of biochemical changes —”genetic alterations,” he called them— caused by the various “drugs of abuse.” These changes could then be defined as “signs of addiction,” enabling “Biology” to establish the “scientific basis” for the manufacture and sale of drugs designed to treat addiction and approved by federal regulators. Leshner estimated the market to be 30-40 million Americans.

In the March 23, 1998 New Yorker Leshner was quoted thus: “My belief is that today, in 1998, you should be put in jail if you refuse to prescribe SSRIs for depression… I also believe that five years from now you should be in jail if you don’t give crack addicts the medications we’re working on now.”

That quote is worth re-reading. The director of NIDA didn't know what the new anti-addiction drugs would consist of, or how they'd work in the brain, or what their side-effects might be... But physicians should go to jail for not prescribing them. That was the true voice of Capital-S Science talking. (When Leshner's Clinton-Era gig at NIDA ended, he was made CEO \of the American Association for the Advancement of Science (AAAS) and Executive Publisher of the journal Science. He retired in 2015.)

Having reported on the marketing of Prozac for the real paper of record, I recognized NIDA's promotion of the Addiction-is-a-Brain-Disease line as part of a long-range marketing plan by pharmaceutical companies developing drugs to treat addiction. Leshner had come to NIMH in 1988 and helped that agency push the idea that Clinical Depression is produced by a “biochemical imbalance” in the brain that could be corrected by a Selective Serotonin Re-uptake Inhibitor, available by prescription. Depression should not be stigmatized, it should be treated. Phrases in Leshner’s pitch for the coming Addiction Meds echoed those used by the Prozac pushers in '88: “A new generation of research based-medications... The ultimate answer lies in Biology... Drug Addiction is a treatable disease...” And we happen to have the treatment in the pipeline and five years from now you'd better be prescribing it or, you know….

The actor Carol O’Connor and his wife attended the event at UCSF looking stunned and mournful. Their son was an addict who had committed suicide and now NIDA was exploiting them to attract media interest in the “Addiction is a Brain Disease” campaign. I recalled a long-ago episode of Archie Bunker’s Place that exposed the effects of speed perfectly. It went something like this: A customer at the bar pays a small debt with some pills. Archie comes home at 3 a.m., calling loudly for Edith. She hurries down the stairs tying her belt and sounding worried. “What’s the matter, Archie?” “Edith, I decided that tonight I’m going to do something for you that you’ve wanted me to do for a long, long time.” She goes “Ooh, Archie,” in a kittenish voice as if anticipating some longed-for pleasure. ”I’m going to paint the back porch.”

I wondered how many in Leshner's UCSF audience remembered him as the federal bureaucrat who would not allow their colleague Donald Abrams, MD, to study the safety and efficacy of marijuana as a treatment for wasting syndrome in HIV patients. And sending this off to the paper of record in February 2021, I wonder how many pot partisans recall that after we passed Proposition in 1996, Alan Leshner took part in the press conference (alongside Barry McCaffrey, Janet Reno, and Donna Shalala) at which the feds threatened to pull the license of any California doctor who approved cannabis use by patients. Drug Czar McCaffrey said of Dr. Tod Mikuriya's practice, “This isn't medicine, this is a Cheech and Chong show.” Leshner said there was no evidence that marijuana was safe or effective as medicine.

Physicians were offended —especially oncologists who understood that marijuana helped people cope with the nausea brought on by chemotherapy, and AIDS specialists who knew it enabled their patients to desire food and to hold it down. An editorial published January 30, 1997 in the New England Journal of Medicine —”Federal Foolishness and Marijuana,” by the editor-in-chief, Jerome Kassirer, MD— called the US government’s policy “misguided,” “hypocritical,” “out of step with the public,” and “inhumane.” The prestigious journal called for rescheduling marijuana so that doctors could prescribe it without fear of reprisal. Kassirer decried “the absolute power of bureaucrats whose decisions are based more on reflexive ideology and political correctness than on compassion.”

Also on January 30, and hardly by coincidence, Harold Varmus, MD, director of the National Institutes of Health, announced that he had asked Alan Leshner to organize a “special conference” on “the public health dilemma” raised by the passage of Prop 215. “I don’t think anyone wants to settle issues like this by plebiscite,” said Varmus. He called instead for “a way to listen to experts on these topics”

The Leshner-invited experts convened for two days in February '97 and they all decreed that “More research is needed” (a truism that is at the same time a lie). It was the beginning of what Dr. Mikuriya called “a stall in the name of science.” That stall continues to this day.

I sent a note to Varmus that probably didn't get through: “Exit polls showed that most people who voted 'yes on 215' did so out of first-hand or second-hand experience. The double-blind, placebo-based clinical trials that scientists consider the 'gold standard' for proving medical efficacy in conditions such as chronic pain, depression and insomnia— ultimately come down to patients declaring whether or not the medicine made them feel better. For these conditions, clinical trials are essentially plebiscites. You helped arrange a stall in the name of science that rationalizes the continuing Prohibition. Your friend Al Gore invoked your expertise when he withheld his support for medical marijuana during the campaign, and it cost him. More research is needed to identify which components of the cannabis plant have which medicinal effects —not to establish its basic safety and efficacy.”