We have an opioid crisis in America. This is not news – and it didn’t begin with the influx of Fentanyl across the Mexican border. That’s only the latest edition of this ongoing problem and the most fatal.

At a recent April subcommittee hearing, Food and Drug Administration Commissioner Robert Califf blamed the pharmaceutical industry for a lack of nonaddictive nonopioid pain medications. In his telling, the FDA is waiting with open arms for any new analgesics that industry may develop: “We need to do everything we can do to push industry and make this happen.”

That’s a noble perspective coming from someone within the industry himself. But there’s much more to this story. Fortunately, we have an insider’s perspective from the pharmaceutical industry. Charles L. Hooper, writing for The Wall Street Journal, formerly worked for Syntex, a large pharmaceutical company. Hooper says this about FDA Commissioner Califf’s statement: “He’s partially right: The government should commit itself to supporting private innovation. But it is disingenuous to blame industry for a dearth of treatments. Consider the evolution of the drug Toradol – generic name ketorolac – a case study in the agency’s propensity to scuttle effective medicine.”

Several decades ago, Syntex discovered and developed ketorolac: a nonsteroidal anti-inflammatory drug, or NSAID, used to provide morphine levels of pain relief without the same abuse potential as opioids. The FDA approved the drug in 1989, and it soon hit the market under the brand name Toradol IV/IM, joining other popular though less potent NSAIDs such as Advil, Motrin, and aspirin.

Before approval, an FDA employee suggested that Toradol IV/IM be given with a loading dose – that is, twice the standard amount. Against their better judgment, Syntex employees complied. The loading dose turned out to be a disaster: Gastrointestinal bleeding killed 97 patients worldwide between 1990 and 1993. The FDA subsequently changed Toradol IV/IM’s label and instructions, eliminating the guidance for double dosages, but by that point the reputational damage had been done.

While injectable Toradol IV/IM continues to be used in emergency rooms and post-op recovery rooms, many physicians remain skeptical of regular doses. When Syntex developed an oral version and submitted it to the FDA, the agency approved it, but gave it a label that essentially precluded its common use – they limited its dosage to about a third of its effective amount and imposed a strict limit of five days usage – also mandating the oral tablets follow an injection or intravenous dose of Toradol IV/IM. In other words, you can’t get Toradol oral treatment from your pharmacist unless you’ve received an injection of it in the emergency room or operating room.

A personal word is warranted here: I have suffered six times in my life with the pain of kidney stones. As anyone who has shared that experience can testify, kidney stones can produce some of the most excruciating pains imaginable. I have received opioid treatments including fentanyl and morphine. While both can be effective, they are usually accompanied by severe constipation – a regular side effect of opioids. Toradol has provided me with the same pain relief as morphine but without the constipation. I carry Toradol tablets in my travel kit and had to use them recently when I experienced another kidney stone during a trans-Atlantic flight.

Hooper says, “A bottle of ketorolac oral tablets should be in almost every American’s medicine cabinet today. It probably never will be. Now that ketorolac is generic, there’s no way to make money on getting the proper dose approved. The FDA could admit that it was wrong and adjust its approval accordingly – but that would require a healthy dose of humility. If Mr. Califf is serious about doing everything to bring beneficial drugs to market, here is a perfect place to start.”

Surprise! Cannabis use has been linked to schizophrenia, especially in young men. This news has been posted in several major news outlets, including The New York Post. The only thing newsworthy about this story is it qualifies as news.

As a physician, I have been aware of this connection since medical school, nearly fifty years ago! But politicians have been pressured to ignore this information since recreational marijuana use has been legalized now in 21 states and 18 more have legalized medical usage. With so many states making it possible to use marijuana, what could go wrong?

I went to college at The University of Colorado in the 1970s. The Boulder campus was filled with potheads and others in the hippie culture. Most of these people were not actually students, but their presence was ubiquitous and the pathology of their minds was undeniable; and that was before the much higher concentrated cannabis was available. Depression and schizophrenia were present then; it’s no surprise they’re even more common today.

The most recent research study was published May 4 in the journal Psychological Medicine. It found that a shocking 30% of schizophrenia cases among men aged 21 to 30 could have been thwarted if they had averted cannabis use disorder (CUD). Scientists examined recent cases of schizophrenia, an abnormal interpretation of reality resulting in hallucinations, delusions or disordered thinking. The study’s authors stated that in 2021, CUD played an integral role in 15% of cases occurring in men aged 16 to 49, and in 4% of cases affecting women in the same age range. This new study examined data concerning 6.9 million people ages 16 to 49 collected in Denmark from 1972 to 2021.

CUD is defined by the Centers for Disease Control and Prevention (CDC) as the inability to stop using marijuana despite negative impacts on one’s health and social life. (That’s a fancy way of saying marijuana is addictive.) According to the CDC, it affects 3 in 10 marijuana smokers. It is not surprising that men are at more risk for developing schizophrenia when smoking marijuana since the same male preponderance is found in non-smokers of marijuana as well.

Excessive use of marijuana in teens is especially dangerous since it can impact brain development and even cause some changes to its anatomy. “The brain is at its peak developmental years from 12 to 20,” said Dr. Scott Krakower, a psychiatrist at Northwell Health’s Zucker Hillside Hospital in an interview with The New York Post. “When marijuana comes into the picture, the normal brain development is impaired.”

“There could be changes to the overall neuroplasticity and neurocircuitry. . . changes to serotonin, changes to dopamine, histamine, all these things are responsible for executive functioning and for how we perceive the world,” he continued. “When cannabis oversaturates the system it can trigger higher levels of anxiety, cognitive delays, and memory loss.” 

Teens are also more likely to develop a problem with the drug. According to a report by the National Institute on Drug Abuse published in March, 2021, those aged 12 to 17 are more apt than those aged 18 to 25 to become addicted to marijuana within a year after using it for the first time.

The Danish study determined that while cannabis use disorder is not responsible for most schizophrenia cases in Denmark specifically, marijuana consumption has contributed to a rise in schizophrenia in the last 50 years. Researchers say one possible reason is that cannabis is both more accessible and more powerful than ever. They found that the amount of THC – the major psychoactive component – in weed in the U.S. rose from 10% in 2009 to 14% in 2019. In Denmark it was 13% in 2006 and 30% in 2016.

For comparison, the THC in weed when I was in college was typically less than 1.5% in the 1970s and 1980s, according to previous research published int the Journal of Forensic Sciences. Today, some cannabis products contain THC concentrations upward of 30%. Some concentrated products such as oils and edibles can have above 95%.

Dr. Krakower says, “A lot of these products are mislabeled. When you’re looking at the weed market, nothing is regulated – you always have to know in the back of your head if you’re having 5mg you might be having 10 or 15 mg- there’s just no way of knowing. The problem is, people forget that marijuana is still a substance no matter how we look at it. Parents need to understand that it’s not healthy.”

That’s not news. I could have told you that 50 years ago!

The standard talking point of many politicians is that pharmaceutical companies are greedy and government should control prices to keep drugs affordable. What is the truth?

Pharmaceutical companies make a lot of money – but they also spend a lot of money to develop their drugs. According to the business services consultancy Deloitte, the average cost of developing a new drug among the top 20 global biopharmaceutical companies rose 15% ($298 million) last year to approximately $2.3 billion. Worse for drug developers, the return on investment reaped by these companies for new drugs and vaccines plunged last year by 82% to 1.2% – the lowest percentage recorded in the 13 years Deloitte launched its annual reports on biopharmaceutical companies R&D – from 6.8% in 2021 and 10.1% in 2010, the first year studied by Deloitte. What other industry would tolerate a 1.2% ROI on a $2.3 Billion investment?

You won’t hear that part of the story in the news because these facts get in the way of the narrative of politicians that the high cost of drugs is due to corporate greed.

Senator Bernie Sanders (D-VT) held a hearing on insulin prices recently and it was contentious, as expected. But Grace-Marie Turner, writing for Galen.org, says it was also surprisingly informative and polite. Top executives of pharmaceutical companies sparred with executives of pharmacy benefit managers (PBMs), pointing fingers over who is responsible for high insulin prices that consumers encounter at the pharmacy. But the debate did illuminate the incredibly complex system of drug pricing.

Eli Lilly Chairman and CEO David Ricks explained that “Lilly hasn’t raised the list price for any of our insulins since 2017, the year I became CEO. In fact, we’ve only cut them.” Their new biosimilar, Humalog, is now available for $25 per vial. Sanofi CEO Paul Hudson said the average net price of Sanofi’s top insulin drug is lower today than it was in 2004 and that his company “returned 84% of our gross insulin sales to payors as rebates.”

The drug companies also are frustrated that the lower-priced version of their drugs seldom make it to PBM formularies. Senators questioned whether the PBMs prefer the higher prices because they get a percentage cut. PBM executives replied they always prioritize the drugs with the lowest price in their complex negotiations with health plans, labor unions, and insurers and pass 98% of rebates along to the customers. PBMs also are revising their formulary schedules to further reduce at-the -counter prices to patients “with an average member out-of-pocket cost below $9 for a 30-day supply of medication,” according to David Joyner, EVP of CVS Health and President, CVS Caremark.

“Today, more than 90% of the prescriptions dispensed are generics and represent a little more than 18% of total spend. And by using competition, generic prices have been deflationary over the last decade,” he said. “Securing affordability for the final 10% of name brand drugs is our focus.” 

Democrats always want to blame the drug companies for high drug prices and always want to solve the problem by government intervention. But Senator Roger Marshall (R-KS) talked about the risks that more government intervention could impede innovation into better products – innovations that continue to extend the life expectancy of diabetics.

Some historical perspective is needed: The first insulins had to be injected multiple times during the day and night, with needles that had to be sharpened, boiled, and reused repeatedly. Today, injections are typically done once a day with throw-away needles that are pre-sterilized and affordable. Blood glucose levels that previously required blood drawing are now available without needle pricks. “The fact is that competition has produced better and better insulin products over time, and we are now seeing prices come down too,” according to Theo Merkel of the Paragon Health Institute in an article for National Review. “Congress should try to address narrow affordability problems where they exist but refrain from soundbite solutions that undermine competition in the long term.”

Unfortunately, the Senate Health, Education, Labor, and Pensions (HELP) Committee couldn’t resist marking up several bills designed to boost competition for generic drugs and increase transparency around PBMs and the insurers that use them. Sen. Rand Paul (R-KY) argued that the committee’s bills are likely to backfire and result in even higher prices.

Just as the Biden Administration repealed all Trump era policies that were effectively limiting illegal border crossings from Mexico, they also repealed a Trump administration solution that addressed the examples Senator Sanders and others raised about patients with lower incomes and no insurance suffering and even dying because they can’t afford their insulin. “A little-noticed policy that would have more directly helped the narrow population that is uninsured or still pays over $35 per prescription was repealed by the Biden administration with little fanfare,” Merkel writes.

He goes on to say, “The Trump administration finalized a rule requiring the nearly 1,400 federally qualified community health centers (FQHCs), which are clinics funded by the federal government to provide community care, to make available insulin at the heavily discounted price they receive under the 340B program (often under $15 per vial) to anyone under 350 percent of the poverty line (roughly $51,000 for a single person).” The option was shut down.

Turner writes, “Despite a sophisticated airing during the hearing of the complex pricing structures and generous patient assistance programs the drug companies offer that even give drugs away to those in need, Sanders concluded by saying ‘There is an enormous amount of greed in the system.”

Never let the facts get in the way of a good political narrative.