CDC Is Worried About Shortages of ADHD Stimulants. What About Rx Opioids?

By Pat Anson

The Centers for Disease Control and Prevention is worried that shortages of stimulant medication used to treat attention-deficit hyperactivity disorder (ADHD) may be forcing some patients to turn to street drugs or even suicide.

In a new report, the CDC estimates that 15.5 million U.S. adults have ADHD¸ a condition that causes inattention, impulsiveness and hyperactivity. About a third of those patients were prescribed a stimulant, but 71.5% of them had difficulty getting their prescription filled because of shortages.

“Shortages of stimulant medications in the United States have affected many persons with ADHD who rely on pharmacotherapy to appropriately treat their ADHD,” wrote lead author Brooke Staley, PhD, an epidemiologist at the CDC’s National Center on Birth Defects and Developmental Disabilities.

“Patients experiencing these difficulties might seek medication outside the regulated health care system, increasing their risk for overdose because of the prevalence of counterfeit pills in the illegal drug market, which might contain unexpected substances such as fentanyl.”

This is the second CDC report in recent months to warn about stimulant shortages. In a CDC Health Advisory released in June, the agency said ADHD patients who are unable to obtain Adderall and other stimulants are at risk of “social and emotional impairment, increased risk of drug or alcohol use disorder, unintentional injuries, such as motor vehicle crashes, and suicide.”

The CDC’s concern about ADHD patients is in marked contrast to its ongoing neglect of pain patients, who face similar shortages of opioid medication.

In a recent PNN survey, 90% of pain patients said they experienced delays or problems getting their opioid prescriptions filled at a pharmacy. Desperate for relief, some bought counterfeit medication or other illicit drugs; obtained opioids prescribed to another person; or used alcohol, cannabis and other substances to ease their pain. Nearly a third said they considered suicide because their pain was so severe.

In short, the very same risky behavior that concerns the CDC about ADHD patients.   

We asked the CDC if it was studying the impact of opioid shortages on pain patients and instead got a defense of the ADHD study.

“There has been limited information about (ADHD) diagnosis and treatment in adults and this analysis aimed to fill that information gap – providing the first national estimates on prevalence of adult ADHD in more than a decade. It is also the first national estimates to describe age at diagnosis and treatment, including telehealth and difficulty filling stimulant prescriptions,” a spokesperson said in an email.

It would not be unreasonable to say that the CDC shares some of the blame for chronic shortages of hydrocodone, oxycodone and other prescription opioids. The agency’s controversial 2016 opioid guideline paved the way for steep cuts in opioid prescribing, resulting in “serious harm” to patients who were rapidly tapered and left in uncontrolled pain. Some committed suicide.

The CDC guideline also greased the skids of opioid litigation by exaggerating the risk of opioid addiction and overdose. Faced with a tsunami of lawsuits, drug distributors and pharmacy chains agreed to ration the supply of opioids at individual pharmacies, and drug makers cut back on the production of opioids to avoid further liability. As recently as last month, Teva Pharmaceuticals stopped production of immediate-release fentanyl medicines, potent pain relievers that were relied on by dying cancer patients.

The CDC has been silent about opioid shortages – so have the FDA and DEA.

“We don't make the medicines and we can't tell someone that they must make medicines. There are some things that are out of our control,” FDA Commissioner Robert Califf, MD, said in a 2023 interview. 

Faced with complaints about shortages of ADHD medication, the DEA recently said it would raise the supply of stimulants that drug makers are allowed to produce in 2025, but would continue with its decade-long campaign to reduce the supply of opioids.

That discrepancy hasn’t been lost on pain sufferers.

“You’ve corrected course for ADHD drugs, now do the same for opioid pain analgesics,” one patient posted in a comment on the DEA’s plan. “Do not cut opioids production in 2025. The shortages across the country will be worse, with a corresponding increase in suffering and deaths among chronic pain patients.”

“These proposals will only further the pain and harm on a community of disabled individuals that did not ask to be disabled,” wrote Rebecca Meadows. “Would you want your mother, brother, sister, child or yourself to suffer unnecessarily due to unwarranted cutbacks in pain medications being made? The amount of people who suffer now is ridiculous but it’s only going to get worse if we continue on this path.”

A former CDC epidemiologist wrote a book about how the CDC’s “Disastrous War on Opioids” made the overdose crisis worse. Opioid overdoses have nearly doubled since the 2016 guideline was released.

“There are still significant restrictions on people in chronic pain for no apparent benefit. There continues to be very high rate of overdoses,” said author Charles LeBaron, MD. “I'm kind of a diehard public health guy. I want to see whether anything good happens. Nothing good happened. Time to reconsider.”

DEA Plans More Cuts in Opioid Supply, While Raising ADHD Stimulant Production

By Pat Anson

The U.S. Drug Enforcement Administration is planning more cuts in the supply of prescription opioids in 2025, while raising production of amphetamine and other stimulants used to treat attention-deficit/hyperactivity disorder (ADHD).

If the DEA’s plans are finalized after a public comment period, it would be the ninth consecutive year the opioid supply has been reduced.

Under the Controlled Substances Act, the DEA has broad legal authority to set annual aggregate production quotas (APQs) for drug makers – in effect telling them how much Schedule I and II chemicals and medications they can produce. DEA sets the quotas after consulting with the Food and Drug Administration (FDA) and other federal agencies, as well as individual states about the projected need for controlled substances.

“FDA predicts that levels of medical need for schedule II opioids in the United States in calendar year 2025 will decline on average 6.6 percent from calendar year 2024 levels. These declines are expected to occur across a variety of schedule II opioids. These declines are expected to occur across a variety of schedule II opioids,” the DEA said in a notice recently published in the Federal Register.

There will not be 6.6% cuts across the board for every opioid. Unlike previous years, the agency is proposing only slight reductions in the supply of fentanyl, oxycodone, hydrocodone and hydromorphone, while keeping quotas unchanged for morphine and codeine.

Most of the cuts are very minor – less than a tenth of one percent -- when the proposed APQ’s for 2025 are compared to the ones adopted in 2024.

DEA Opioid Production Quotas for 2025

• Fentanyl: 0.0025% decrease

• Oxycodone:  0.137% decrease

• Hydrocodone: 0.081% decrease

• Hydromorphone: 0.015% decrease

• Morphine: Unchanged

• Codeine: Unchanged

The DEA notice does not address the discrepancy between the FDA’s estimate of a 6.6% decline in medical need for opioids with the quotas it is proposing. The agency says it considered a “potential increase in demand for certain opioids” due to more elective surgeries being performed in 2025. Many of those surgeries were postponed during the COVID-19 pandemic.

The FDA predicted a 3.5% increase in domestic medical use of Schedule II stimulants in 2025. Demand for stimulants to treat ADHD has grown in recent years, but the drugs are also increasingly used to treat brain fog and fatigue caused by Long Covid. The FDA told DEA it was concerned about ongoing shortages of amphetamine, lisdexamfetamine, and methylphenidate, which are used to make stimulants such as Adderall.    

The DEA wants to raise production quotas for amphetamine (+5.9%) and lisdexamfetamine (+23.5%), while leaving the 2025 quota for methylphenidate the same as it was in 2024. The agency said inventories of amphetamine and methylphenidate-based products had increased, while shortages of lisdexamfetamin continue.

“DEA believes that manufacturers will be able to meet the increase in domestic medical need for these three schedule II stimulants with the APQs proposed in this notice,” the agency said.

The Myth of Opioid Diversion

The DEA has been cutting opioid production quotas for nearly a decade, reducing the supply of oxycodone by over 68% and hydrocodone by nearly 73% since 2015. Many of those cuts are due to pressure from Congress, as well as a common belief that prescription opioids are often diverted or sold to people they are not intended for.

That belief is largely a myth.

As required by Congress, DEA estimated the diversion rate of schedule II opioids in 2025, and once again came to the conclusion that diversion is rare – less than half of one percent for oxycodone and hydrocodone. Much of the diversion is a result of theft and losses in the supply chain, before opioids even reach patients.

Estimated 2025 Diversion Rates

• Oxycodone: 0.493%

• Hydrocodone: 0.379%

• Fentanyl:  0.013%

• Hydromorphone: 0.06%

The DEA’s diversion rates are partially based on “red flag” data from prescription drug monitoring programs (PDMP). Potential red flags include patients who see three or more prescribers in a 90-day period; patients who receive a daily opioid dose in excess of 240 morphine milligram equivalents (MME); and patients who pay in cash for a controlled substance.

DEA requested PDMP data from all 50 states, but only 29 states responded to the request by sharing summaries of their red flag data.

“While PDMP data is useful in estimating diversion, it is not conclusive. Further investigation would be required before concluding that any of the subject prescriptions were actually diverted. DEA continues to evaluate its methodologies in estimating diversion in an effort to set quotas more efficiently. State participation is crucial to accurate data analysis, and DEA anticipates working closely with states, as well as other federal and state entities, in future quota determinations,” the agency said.

Public Comments

The DEA quietly published its notice about 2025 production quotas in the Federal Register on September 25, with no fanfare or press release.

Usually the agency receives thousands of comments from the public about its production quotas, but so far there have been only a handful of comments posted. Many are from patients still bitter about the decade of cuts the DEA has imposed on the opioid supply, which have contributed to record shortages of prescription drugs.

“The actions that are being taken by Congress, by the DEA, state legislatures, and state medical boards, have caused THOUSANDS of these patients to lose access to their medications, have resulted in the improper prosecution of pain doctors, resulting in a severe nationwide shortage of pain specialists, and nationwide shortages of medications,” wrote David Smith.  

“The CDC, FDA, and DEA have severely underestimated the needs of chronic pain patients and misjudged the consequences of these cuts. While opioid misuse is a serious issue, penalizing legitimate pain patients is not the solution,” said Gina Harrison.

“Please I'm begging you not to cut opioids meds this year,” said Melissa Guthrie. “I'm on palliative care and there were a couple months last year I didn't get my meds due to shortages. You know it's not the pain meds causing harm. It’s the illicit fentanyl and street drugs killing people.”

You still have time to make your feelings known, as long as you do it by October 25, when the public comment period ends. To make a comment, click here.

Prescription Opioids Play Only Minor Role in Overdose Crisis

By Pat Anson, PNN Editor

The role of prescription opioids in the nation’s overdose crisis continues to shrink.

In a new study from the drug testing firm Millennium Health, researchers say multiple substances were found last year in nearly 93% of urine samples in which fentanyl was detected. That is not altogether surprising, as “polysubstance” use increased as fentanyl came to dominate the illicit drug supply, appearing in more and more street drugs such as heroin, cocaine and methamphetamine.

What is surprising is the minimal role that prescription opioids now play. In 2013, opioid pain medication was the most common substance found in fentanyl-positive drug tests in the United States, appearing in over 70% of urine samples.  A decade later, prescription opioids were detected in less than one in ten samples — ranking far behind methamphetamine, cannabis, cocaine and heroin.

In fact, you are about twice as likely to find two other medications -- benzodiazepines (15.8%) and gabapentin (13.3%) -- than you are prescription opioids (7.6%) in urine samples testing positive for fentanyl.

Substances Detected in Fentanyl-Positive Drug Tests (2023)

MILLEnNIUM HEALTH

Millennium based its findings on over 4.1 million urine drug tests (UDTs) collected from 2013 to 2023 and analyzed through mass spectrometry. Because many of those samples came from people being treated for a substance use disorder, they offer a clear insight into drug trends that are driving the overdose crisis.

Now in its “fourth wave,” Millennium says a tidal shift has occurred in the so-called opioid epidemic, with illicit drug users far more likely to use non-opioid substances like stimulants than prescription opioids.

“National, regional, and state-level UDT data all suggest that people who use fentanyl are now, intentionally or unintentionally, much more likely to also use methamphetamine and cocaine,” the report found. “The results of our analyses also reveal shifting patterns of opioid use among those who use fentanyl. More specifically, they showed progressive declines in prescription opioid use from 2015 to 2023.”

The declining role of prescription opioids can be traced back to the 2016 CDC opioid guideline and a multiyear campaign by the DEA to slash opioid production quotas, which has reduced the supply of oxycodone and hydrocodone by about two-thirds. There is little evidence either of those federal efforts reduced the number of overdoses. The CDC estimates there were over 111,000 drug deaths in the 12-month period ending in September 2023 — nearly double the number of fatal overdoses in 2016.

The growing use of stimulants such as methamphetamine makes it difficult for public health campaigns to address the problem. Unlike opioids, there are no FDA-approved medications for stimulant use disorder, leaving behavioral therapies and abstinence as the only “evidence-based” treatments for people with a stimulant problem.

“Stimulants are a serious national challenge emphasizing the need for continued progress on the national plan to address methamphetamine supply, use, and consequences,” Millennium said.

‘Safe Supply’ of Rx Opioids Saved Lives in British Columbia

By Pat Anson, PNN Editor

Prescribing opioids and other medications to people with substance use disorders significantly reduces their risk of dying, according to a large new study in British Columbia. The findings add weight to efforts to create a “safe supply” of legal medications for patients at risk of an overdose from increasingly toxic street drugs.

Vancouver, British Columbia was the first major North American city to be hit by a wave of overdoses involving illicit fentanyl, a potent synthetic opioid. That led Vancouver to become a laboratory for harm reduction programs and safe supply sites offering prescription opioids and injectable heroin to drug users.  

How effective have those programs been?

A study by the B.C. Centre for Disease Control, recently published in the British Medical Journal, found that prescribing opioids, stimulants and anti-anxiety medication to nearly 6,000 drug users dramatically reduced their risk of death.

The Risk Mitigation Guide (RMG) program was initially launched in early 2020 to help drug users going through withdrawal while isolated by the COVID-19 quarantine. A year later, the program was extended, allowing doctors and nurse practitioners to prescribe hydromorphone, morphine, oxycodone, fentanyl, benzodiazepines and stimulants to drug users.

People who were given an initial dose of prescription opioids had a 61% lower risk of death from any cause the following week, and were 55% less likely to die of a drug overdose.

The protective effect of a safe supply increased as more doses were provided. Drug users who received four or more days of opioids were 91% less likely to die from any cause and 89% less likely to die from an overdose.

"We saw a profound impact on reduction in somebody's overdose death risk the week after they picked up these drugs, to a degree that is really surprising and has enormous potential," co-author Paxton Bach, MD, an addiction medicine specialist, told CBC News. "This paper is the strongest evidence we have so far, by a large margin, supporting the idea that this can be an effective strategy for reducing overdose death risk."

But critics of safe supply programs say they don’t really reduce drug abuse. An investigation last year by the National Post found that hydromorphone pills given to drug users in Vancouver were being sold to other addicts, with the sellers then using the money to buy more potent street drugs that were often laced with fentanyl.

A new study in JAMA Internal Medicine also found that opioid-related hospitalizations rose sharply in British Columbia after safe supply programs were launched there, although there was no significant change in overdose deaths. The spike in hospitalizations may have been due to more potent street drugs and counterfeit pills on the black market.

Since a public health emergency was declared in British Columbia in 2016, over 13,000 people have died from drug overdoses. A 2020 analysis found that only about 2% of the B.C. opioid-related deaths were caused by prescription opioids alone. The other overdoses mainly involved illicit fentanyl and other street drugs.  

Stimulants Involved in Growing Number of Fentanyl Overdoses

By Pat Anson, PNN Editor

The number of drug deaths involving both fentanyl and stimulants has soared in recent years, according to a new UCLA study that highlights the complex and changing nature of the U.S. overdose crisis.

Stimulants such as cocaine and methamphetamine are now involved in nearly a third of fentanyl-related overdoses, the most of any other drug class. Fentanyl is a synthetic opioid up to 100 times more potent than morphine and 50 times as potent as heroin.

In 2010, researchers say there were only 235 fatal overdoses in the U.S. involving illicit fentanyl and stimulants. In 2021, there were 34,429 drug deaths linked to fentanyl and stimulants, a 14,550% increase in a little over a decade.

"We're now seeing that the use of fentanyl together with stimulants is rapidly becoming the dominant force in the US overdose crisis," said lead author Joseph Friedman, PhD, an addiction researcher at the David Geffen School of Medicine at UCLA. "Fentanyl has ushered in a polysubstance overdose crisis, meaning that people are mixing fentanyl with other drugs, like stimulants, but also countless other synthetic substances. This poses many health risks and new challenges for health care providers.

“We have data and medical expertise about treating opioid use disorders, but comparatively little experience with the combination of opioids and stimulants together, or opioids mixed with other drugs. This makes it hard to stabilize people medically who are withdrawing from polysubstance use."

People who overdose on stimulants and other non-opioid substances mixed with fentanyl may not be as responsive to naloxone, which only works as an antidote to opioids.

The study findings, published in the journal Addiction, highlight the four “waves” of the overdose crisis, which began with an increase in deaths from prescription opioids (Wave 1) in the early 2000s, followed by a rise in heroin deaths (Wave 2) in 2010, and fentanyl-related overdoses in 2013 (Wave 3). The fourth wave — overdoses from fentanyl and stimulants — began in 2015 and continues to escalate.

The Four Waves of Overdose Crisis

SOURCE: ADDICTION

Since cocaine, methamphetamine and other stimulants are not opioids, the findings undercut the long-held theory that the overdose crisis started with prescription opioids and is still being fueled by people addicted to them. Deaths involving prescription opioids and heroin have been in decline for several years.

Researchers found that fentanyl/stimulant deaths disproportionately affect African Americans and Native Americans. There are also geographical patterns to fentanyl/stimulant use. In the northeast US, fentanyl is usually combined with cocaine, while in the south and western US, fentanyl is most commonly found with methamphetamine.

"We suspect this pattern reflects the rising availability of, and preference for, low-cost, high-purity methamphetamine throughout the US, and the fact that the Northeast has a well-entrenched pattern of illicit cocaine use that has so far resisted the complete takeover by methamphetamine seen elsewhere in the country," Friedman said.

In addition to its low cost, drug users say methamphetamine helps prolong fentanyl’s “high” and delays the onset of withdrawal symptoms.  

Counterfeit pills laced with fentanyl – which are frequently made to look like oxycodone or alprazolam (Xanax) – represent about a quarter of all illicit fentanyl seizures. Researchers say it is difficult to track deaths involving counterfeit pills because they are often mistaken for legitimate medication, so the data is not completely reliable.

In its most recent update on the overdose crisis, the CDC estimates there were a record 111,355 drug deaths in the 12-month period ending April 2023 -- about a thousand more deaths than the year before. Fentanyl and its analogues were involved in nearly 70% of the overdoses, stimulants were linked to about a third of them, and cocaine was involved in about a quarter of the drug deaths.

Illicit Drug Users Turn to Cannabis as ‘Safe Supply’ Option

By Pat Anson, PNN Editor

The cannabis industry and its advocates have long said that medical marijuana could help solve the opioid crisis by reducing demand for prescription opioids. While the evidence for that claim is somewhat mixed, a new study suggests that cannabis may be useful in reducing demand for illicit opioids, such as fentanyl.

Researchers at UCLA and the British Columbia Centre on Substance Use surveyed 205 people in Vancouver, BC who use cannabis and “unregulated opioids” obtained on the black market. In recent years, Vancouver has become a laboratory for harm reduction programs aimed at reducing overdoses, such as “safe supply” sites that offer prescription opioids and injectable heroin to drug users.  

The survey findings, published in the International Journal of Drug Policy, found that almost half the participants used cannabis to manage their opioid cravings and nearly 58% reported decreasing their opioid use. Researchers say the association between cannabis and harm reduction was “mainly driven by those living with moderate to severe pain.”

“These findings indicate that cannabis use to manage opioid cravings is a prevalent motivation for cannabis use among PWUO (people who use unregulated opioids) and is associated with self-assessed reductions in opioid use during periods of cannabis use,” wrote lead author Hudson Reddon, PhD, a Postdoctoral Fellow at the BC Centre on Substance Use.

The study is believed to be the first to investigate if illicit drug users can successfully manage their opioid cravings with cannabis. If the findings are confirmed, it could broaden access to cannabis as a harm reduction measure.

A previous survey of illicit drug users by the BC Centre on Substance Use found that about 1 in 4 used cannabis for harm reduction. About half used cannabis as a substitute for cocaine, methamphetamine and other stimulants (50%) and nearly a third used it as a substitute for illicit opioids (31%). Other reasons for using cannabis include coming off of other drugs (25%), substitution for a legal substance (15%), and as a treatment for withdrawal (15%).

“Given the increasing harm of the drug toxicity crisis and ongoing maturation of the regulated cannabis market in Canada, evaluating how cannabis use patterns, such as substitution, impact opioid use behaviours will be important to inform public health and policy responses to mitigate the harms of opioid use and evolving cannabis access,” Reddon wrote.

“Increasing the accessibility of cannabis products for therapeutic use may be a useful supplementary strategy to mitigate exposure to unregulated opioids and associated harm during the ongoing drug toxicity crisis.”

FDA and DEA Leaders Call for More ADHD Meds, But Ignore Rx Opioid Shortages

By Pat Anson, PNN Editor

Leaders of the Food and Drug Administration and the Drug Enforcement Administration say they’re working to end one of the worst drug shortages in decades.

“The lack of availability of certain medications in recent months has been understandably frustrating for patients and their families,” FDA commissioner Robert Califf, MD, and DEA Administrator Anne Milgram said in an unusual joint letter. “We are calling on key stakeholders, including manufacturers, distributors, pharmacies, and payors, to do all they can to ensure access for patients when a medication is appropriately prescribed.”

Those should be welcome words for pain patients across the U.S. who have trouble getting their prescriptions filled for opioid medication. Unfortunately, the letter has nothing to do with opioids. It’s only about shortages of Adderall and other prescription stimulants, which are used primarily to treat attention-deficit/hyperactivity disorder (ADHD).

The letter is the latest example of how the FDA and DEA have turned a blind eye to opioid shortages, which both agencies have played prominent roles in creating. Two widely used painkillers, oxycodone and hydrocodone, have been difficult to get for months, leaving thousands of patients in uncontrolled pain or going into withdrawal. Even big chain pharmacies like CVS are out of opioids or have a limited supply.   

“I had to once again follow up with CVS, just to be told they received absolutely nothing! Pain management provider in response sent another prescription to the outpatient pharmacy,” says Christine Kucera, a pain patient who recently wrote a column for PNN about her problems getting prescriptions filled for oxycodone.

“I'm currently sitting in the waiting area at the outpatient pharmacy, stressing, waiting for another bomb to drop.”

The American Society of Health-System Pharmacists (ASHP) first warned about a shortage of immediate release oxycodone in March. Over the next few months, hydrocodone/acetaminophen tablets (Vicodin) and oxycodone/acetaminophen tablets (Percocet) were added to the ASHP’s shortage list. Those shortages could soon grow even worse, because one of the largest generic drug makers in the world, Teva Pharmaceutical, is discontinuing production of immediate release oxycodone. 

Despite these warning signs, the FDA and DEA have yet to acknowledge shortages of either oxycodone or hydrocodone, and appear to be doing nothing about them. But they are moving to boost production of stimulants used to treat ADHD. The agencies say drug makers have sold only 70% of the stimulants they were authorized to produce.   

“We want to make sure those who need stimulant medications have access,” Califf and Milgram said in their letter. “We have called on manufacturers to confirm they are working to increase production to meet their allotted quota amount.” 

“What this latest notice shows is that the FDA and DEA could get involved with the opioid shortage if they wanted to,” says Rick Martin, a retired pharmacist disabled by back pain. Martin recently had to switch to a weaker opioid for pain relief because he can’t find a pharmacy with hydrocodone in stock.

“Teva said they were going to stop making oxycodone. The DEA/FDA could be proactive and ask Teva to relinquish their remaining 2023 quota allotment, then redistribute to other manufacturers,” Martin told PNN. 

Lower Production Quotas

The DEA sets annual production quotas for opioids, stimulants and other controlled substances, working closely with the FDA in assessing demand. Last year, the FDA advised the DEA that demand for hydrocodone, oxycodone and other Schedule II opioids would fall by 5.3% in 2023, which resulted in another year of cuts by the DEA in opioid production. Since 2013, the supply of oxycodone has fallen by 65 percent and hydrocodone by 73 percent. 

The FDA also advised the DEA that domestic medical use of stimulants would fall by 0.1% in 2023, even while warning that shortages were developing. The DEA’s response last December was that amphetamine and other stimulants were overprescribed to patients who didn’t really need them, and that its proposed production quotas (APQ) for the drugs in 2023 would be adequate.

“The majority of the manufacturers contacted by DEA and/or FDA have responded that they currently have sufficient quota to meet their contracted production quantities for legitimate patient medical needs,” the DEA said in the Federal Register. “Based on this trend, DEA has not implemented an increase to the APQ for amphetamine at this time.”

That kind of background detail is missing from Califf’s and Milgram’s letter, which disingenuously claims that there is little that the DEA and FDA can do to ensure that there are adequate supplies of medication. 

“This is not a problem that the FDA and DEA can solve on our own,” Califf and Milgram wrote. “The FDA and DEA do not manufacture drugs and cannot require a pharmaceutical company to make a drug, make more of a drug, or change the distribution of a drug.” 

Only briefly do Califf and Milgram acknowledge that their own production quotas are part of the problem, saying they were “committed to reviewing and improving our quota process.” 

“These (stimulant) shortages were caused by the DEA, which limited the manufacture of these medications,” says Andrea Anderson, a pain sufferer and patient advocate. “This exact problem has affected patients who require opioid analgesics to manage their severe pain. It has been affecting them for over six years, yet we see no mention of the extraordinary difficulties these patients are experiencing trying to find pain medication.  

“The DEA has no reason to be involved in deciding how many prescriptions should be written for any medical condition. This is the purview of trained medical clinicians and quantities should not be dictated by law enforcement agencies.” 

Drug manufacturers are required to report shortages and supply interruptions to the FDA. Doctors, hospitals, pharmacies and consumers can also report supply problems by sending an email to drugshortages@fda.hhs.gov.

That’s where Christine Kucera recently sent an email addressed to the FDA commissioner.

“Three different medications used in my treatment are continuously unavailable, sometimes for weeks and months. CVS IS OUT, the system is not working, and all you do is NOTHING!” Kucera wrote to Califf. 

“When will you address the unethical treatment and harms being inflicted upon millions of US citizens directly caused by government practicing medicine, limiting and denying access to essential medicines based on biased and manipulated facts, reduced quotas, faulty CDC prescription guidelines that should never have been created; and the DEA who are making up their own rules, practicing medicine, and deciding what they think appropriate medical care is?”  

Why Intractable Pain Treatment Requires a Stimulant

By Dr. Forest Tennant, PNN Columnist

In 1896, Dr. Henry Snow was the chief cancer surgeon at the Royal Brompton Hospital in London. He recognized and agonized over the immense pain and suffering of his patients when they developed constant pain and approached their end of life.

Dr. Snow wanted to relieve their suffering, so he administered the drugs that were available one at a time: morphine, cocaine and alcohol. With each he managed to get some pain relief, but didn’t obtain the relief he wanted and patients were still suffering. Not to be deterred, he made a profound discovery.

Dr. Snow mixed morphine and cocaine in liquid alcohol and administered the solution to his patients. Then he found formidable and humane pain relief. This three-drug mixture gave rise to the concept of “synergy of constituents,” which means that the simultaneous administration of multiple pain-relieving drugs added up to more than each one alone. In other words, two and two equaled six rather than four. 

The success of Dr. Snow’s discovery spread rapidly to other hospitals and countries, and became known as the “Brompton cocktail.” In France and elsewhere, physicians discovered they could add an antihistamine, antipsychotic or cannabis oil to the mixture and get even more pain relief.  

The Brompton cocktail was used until the 1970’s, when it gave way to the convenience of opioid tablets, capsules and injections, rather than the time and cost of making a liquid that contained multiple drugs. 

The Amphetamine Discovery 

Fortunately, after the demise of the Brompton cocktail, a handful of researchers weren’t about to forget the “synergy of constituents” and the pain-relieving potency of stimulants like cocaine. An example of the pain-relieving capability of stimulants is caffeine, which in the 1960’s was added to a variety of pain relievers such as aspirin and codeine to obtain synergy. 

Amphetamine was discovered in the 1930’s and promoted as “Benzedrine” to stay awake while driving. Because amphetamine produced alertness, it became known as a stimulant. Clinical reports began to surface in the 1940’s that amphetamine and its derivatives also helped depression, weight loss, mental alertness, hyperactivity and attention span. They soon began to be marketed and labeled for those conditions.  

Clinical studies on amphetamine derivatives for pain relief were finally started in the 1980’s, and they clearly showed that they provided a great deal of pain relief.  

By the time the last century folded, a core of pain researchers knew that not only cocaine but amphetamine derivatives such as methylphenidate and phentermine relieved pain. What they didn’t know was why. This answer was to come 15-20 years later. 

Stimulants Initially Rejected 

I became quite excited about the clinical trials that showed stimulants relieved pain, and in the late 1990’s gave a group of intractable pain patients the weak stimulant and weight loss drug phentermine, in combination with clonidine. The opioid dosages for these patients dropped 40 to 50 percent within six weeks and they got even better pain relief.

I presented my findings to colleagues at some national professional meetings. Much to my surprise, I was summarily informed that the new long-acting opioid formulations of the fentanyl patch (Duragesic), oxycodone (Oxycontin), morphine (MS Contin) and the implanted intrathecal (spine) opioid pump eliminated any need for stimulants or the concept of “synergy of constituents.”

By the turn of the century, the use of these new long-acting opioids and implanted opioid pumps became the standard of the day. Stimulants and their synergy were essentially forgotten, and they were rarely used for intractable pain again until about 2010. 

The Rebirth of Synergy 

After the year 2000, I don’t recall ever being referred an intractable pain patient who had not already been started on one of the long-acting opioids and/or an implanted opioid pump. They were referred to me simply because they were not getting adequate pain relief. Almost every one of these patients had found that their opioids quit working well, regardless of dosage or even if a second or third opioid was added to the mix.  

Somewhat out of desperation, about 12 years ago I recalled Dr. Snow, the Brompton cocktail and the “synergy of constituents.” I also remembered my study on phentermine and clonidine, so I started giving patients on opioids who were doing poorly my favorite stimulant, phentermine, or occasionally methylphenidate (Ritalin).  

Later the narcolepsy drug modafinil (Provigil) and a mixture of amphetamine salts (Adderall), came on the market. They too proved to be excellent “synergists” with opioids. I found that every intractable pain patient who received one of these stimulants not only got better pain relief and were either able to “hold the line” or reduce their opioid dosage.  

Phentermine continued to be my favorite stimulant to relieve pain and reduce the use of opioids because it additionally kept weight down and helped the patient keep moving and functional. 

Why Stimulants Work 

Although stimulants have been clinically known to relieve pain since Dr. Snow’s experiments in 1896, researchers didn’t provide us with the biologic “why” until recently. 

In the past decade, some outstanding researchers determined that there are about half a dozen different neurotransmitters in the brain and spinal cord that relieve pain. The three major neurotransmitters are endorphin, dopamine and gamma amino butyric acid (GABA). These neurotransmitters relieve pain by activating trigger points in the central nervous system called receptors. 

These astute researchers also determined that intractable pain may deplete endorphin, dopamine and GABA. Consequently, a substitute drug may have to be administered to obtain adequate pain relief.  

If you have constant, intractable pain, you may likely need the “synergy of constituents,” which will include an opioid, stimulant, and GABA substitute. Popular GABA substitutes include diazepam (Valium), carisoprodol (Soma), pregabalin (Lyrica), gabapentin (Neurontin), clonazepam (Klonopin), topiramate (Topomax) and alcohol. 

Which Patients Should Receive a Stimulant?

Stimulants have well-known abuse and addiction potential, so they should only be given to patients who have a well-documented disease or injury that is known to cause severe intractable pain. The most common diseases in this category are adhesive arachnoiditis, stroke or head trauma, reflex sympathetic dystrophy (RSD/CRPS), Ehlers-Danlos syndrome, and some autoimmune-collagen disorders.  

In most cases, patients who need a stimulant are clearly debilitated and require some family and caretaker support to function and carry out activities of daily living.  

Intractable pain patients have several dopamine substitutes available: 

• Amphetamine Salts (Adderall)

• Methylphenidate (Ritalin)

• Dextroamphetamine

• Phentermine

• Phendimetrazine

Misunderstood Objections

Many medical practitioners are not yet aware of the new research on stimulants and hesitate to prescribe them, even to needy, legitimate patients. The fear of abuse, diversion or dependence by the intractable pain or palliative care patient, while understandable, should not cause reluctance to prescribe a stimulant to these patients. No intractable pain patient will give away something that works so well.

In addition, the dosage of stimulants for pain relief is considerably lower than the usual level needed for abuse. Only small dosages are clinically needed in most cases and pharmacies today only issue limited quantities. Another safety factor in controlling adverse consequences of stimulants is that the severe intractable pain patient will usually have close family or caretaker support who can safely store and administer stimulants.

There is an unfounded fear of hypertension if a stimulant is prescribed. This is rarely the case, since the pain patient is dopamine deficient. A stimulant drug in an intractable pain patient may actually lower blood pressure since it may be elevated due to pain.

There is the belief that Adderall, Ritalin and some other stimulants are only for attention deficit hyperactivity disorder (ADHD). What is misunderstood is that ADHD is universal among intractable pain patients. Every person with intractable pain has reduced attention span, hypertension and agitation. One could argue that every intractable pain patient should be on a stimulant just for their ADHD. 

Dr. Snow and the Royal Brompton Hospital had the right idea. The severe, intractable pain patient needs an opioid to replace endorphin, a stimulant to replace dopamine, and a substitute for GABA.  

It’s time we bring back the “synergy of constituents” to humanely get better pain relief and simultaneously lower opioid dosages in the intractable pain patient. 

Forest Tennant, MD, DrPH, is retired from clinical practice but continues his studies on the treatment of intractable pain through the Arachnoiditis Research and Education Project. A bibliography on stimulants for intractable pain treatment can be found here  

The Tennant Foundation gives financial support to Pain News Network and sponsors PNN’s Patient Resources section.   

Focus on Opioid Crisis Overlooks Rise in Stimulant Deaths

By Pat Anson, PNN Editor

While much of the nation was focused on the opioid crisis, new research shows that another drug epidemic was taking the lives of U.S. military veterans.

University of Michigan researchers say the rate of veteran overdose deaths involving cocaine, methamphetamine and other stimulants tripled from 2012 to 2018. Most of the veterans did not receive any substance abuse treatment in the year before they died.

“We have been so focused on opioids that we are missing the tremendous increase in people who are using multiple substances, as well as those using stimulants only, when we know that many people don’t stick to just one substance,” says lead author Lara Coughlin, PhD, a psychologist and an assistant professor in the U-M Department of Psychiatry. “The fact that so many of those who died of an overdose had not received substance use disorder treatment is especially concerning.”

Coughlin and her colleagues reviewed the medical records of 3,631 veterans who died from overdoses involving stimulants, and found that about two-thirds of the deaths involved cocaine. Over half of the stimulant deaths (54.1%) also involved another substance, usually alcohol or an illicit opioid such as heroin or fentanyl. Prescription opioids were involved in less than 26% of the stimulant-related overdoses.

Researchers called the tripling of stimulant deaths “an escalating public health crisis” that deserves more attention.

“Recent trends show stark increases in stimulant-involved overdoses, with the majority of these overdoses deaths involving multiple classes of substances. These more complex, polysubstance-involved overdose deaths necessitate an expansion from a singular opioid-centric focus to include other substances and consideration of the role of stimulant use on overdose risk to inform effective prevention and treatment efforts,” researchers reported in the journal Addiction.

The authors noted there are few medication-based treatments to help people reduce their use of methamphetamine or cocaine, while multiple medications are available to treat those with opioid or alcohol use disorders.

Better access to treatment was especially needed for veterans in rural areas and those who are homeless. About one-third of all the overdose deaths involving stimulants were in Black veterans, as were two-thirds of the deaths from cocaine alone.

In addition to the risk of overdose, researchers say people who use methamphetamine or cocaine are at greater risk of heart damage. About 62% of the overdoses involving stimulants were among veterans aged 45 to 64.

“We need to build better awareness of the role of stimulants as a risk factor for overdose, and of the need for those who have stimulant use disorders to be referred for treatment, regardless if they are also using opioids,” said Coughlin. “We know that cocaine and methamphetamine are much more likely to be adulterated with fentanyl or other synthetic opioids now, so those who use them need to be equipped with rescue doses of naloxone to use and need to know about the risk for overdose in case they or someone they’re with experiences an unexpected, life-threatening reaction.”

The rise in stimulant deaths has not occurred in a vacuum. In the first half of 2019, data from 24 states and the District of Columbia showed that stimulants were involved in 5 out of 11 fatal overdoses. The CDC issued a Health Alert Network Advisory last year about a record number of overdoses, due in part to an acceleration in stimulant-related deaths.