Feds Funding Study of Cannabis as Opioid Alternative

By Pat Anson, PNN Editor

Columbia University has been awarded a grant from the National Institute on Drug Abuse (NIDA) to investigate whether medical cannabis can reduce the use of opioids and overdose risk in chronic pain patients.  

The grant was awarded after researchers with Columbia Care completed a small pilot study that found nearly two-thirds of patients with chronic nerve pain were able to reduce or stop their opioid use. Columbia Care is a private medical marijuana company not affiliated with the university that operates a chain of cannabis dispensaries around the country.

“There is an urgent need to investigate the potential impact of cannabinoid use on limiting opioid overdose risk and to determine whether specific products are more beneficial for certain populations of patients with pain and opioid use,” said Arthur Robin Williams, MD, a professor in the Division on Substance Use Disorders in the Columbia University Department of Psychiatry.

The pilot study involved 76 neuropathy patients in New York State who were given Columbia Care’s dose-metered cannabis products for nine months. By the end of the study, 62 percent of the patients were able to reduce or stop using opioid pain medication.

Columbia Care makes a variety of medical cannabis products that come in tablets, tinctures, suppositories, topical formulations or can be used in vaporizers. 

“We have seen through this pilot study the power of our proprietary formulations to reduce our patients’ dependence on opioids in a defensible, scientific manner,” said Rosemary Mazanet, MD, chief science officer and chair of the scientific advisory board at Columbia Care.

DRUG POLICY ALLIANCE

DRUG POLICY ALLIANCE

Although medical marijuana is often touted as a possible solution to the nation’s opioid crisis, research findings so far have been mixed.

A recent study by the RAND Corporation found little evidence that states with medical marijuana laws see reductions in legally prescribed opioids. While some pain patients may be using or experimenting with medical marijuana, RAND researchers do not believe they represent a significant part of the opioid analgesic market.

"If anything, states that adopt medical marijuana laws... experience a relative increase in the legal distribution of prescription opioids,” researchers found.

Another study of Medicare and Medicaid patients found that prescriptions for morphine, hydrocodone and fentanyl dropped in states with medical marijuana laws, while daily doses for oxycodone increased. A second study found a 6% decline in opioid prescribing to Medicaid patients in states with medical marijuana laws.  Both studies were conducted during a period when nationwide opioid prescribing was already in decline.

A 2014 study published in JAMA Internal Medicine found that opioid overdoses declined by nearly 25 percent in states where medical marijuana was legalized.

Rx Drug Monitoring Not Reducing Opioid Abuse

By Pat Anson, Editor

Prescription drug monitoring programs (PDMPs) have long been promoted as a critical tool in the fight against opioid abuse and overdoses. PDMP’s in 49 states and the District of Columbia allow physicians and pharmacists to consult a prescription drug database to see if patients might be “doctor shopping” or selling their opioid medication.

But a new study has found little evidence that PDMPs are working and that they may in fact be driving some patients to the black market for cheaper drugs such as heroin.

Researchers at Columbia University's Mailman School of Public Health and University of California, Davis, analyzed 17 studies that looked at the effectiveness of PDMPs. Their findings are published online in the Annals of Internal Medicine.

“Evidence that PDMP implementation either increases or decreases nonfatal or fatal overdoses is largely insufficient, as is evidence regarding positive associations between specific administrative features and successful programs. Some evidence showed unintended consequences,” wrote lead author David Fink, MPH, a doctoral candidate in epidemiology at the Mailman School of Public Health.

What were those unintended consequences? Three studies that looked at heroin related overdoses found a “statistically significant” increase in heroin deaths after PDMPs were implemented.

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"This suggested to us that heroin substitution may have increased after PDMP-inspired restrictions on opioid prescribing," says Silvia Martins, MD, a professor of epidemiology at Mailman and co-senior author. "We therefore caution that programs aimed at reducing prescription opioids should also address the supply and demand of illicit opioids."

Researchers believe that efforts to reduce doctor shopping and the diversion of prescription opioids may have backfired.

“A reduction in black market prescription opioids, although generally viewed as positive, also may generate unanticipated outcomes. For example, an ethnographic study of high-risk users in Philadelphia and San Francisco found that key drivers of the progression from prescription opioid to heroin use are the rising cost of the ‘pill habit’ and heroin’s easy availability and comparatively lower cost,” Fink said.

Heroin overdoses also rose after Purdue Pharma introduced a new and more expensive abuse deterrent formulation of OxyContin in 2010. According to one study, each death that was prevented by OxyContin's reformulation “was replaced with a heroin death.”

Fink and his colleagues say more studies are needed to examine the true effectiveness of PDMPs, which can vary widely from state to state.

Doctor Shopping Rare

Missouri is the lone state that has not adopted a statewide PDMP and one family physician would like to keep it that way.

In an unpublished study, John Lilly, DO, claims that PDMPs are not working because doctor shopping is rare to begin with. In 2016, doctor shopping was responsible for only 1.7% of all misused opioid prescriptions. The rest are stolen, borrowed or bought on the black market, or misused by the patients they were prescribed to.

“The prescription drug monitoring programs will never catch the remaining 98.3 percent of the problem. That is why the death rate has not decreased despite 49 states having an operational PDMP,” Lilly wrote.  “There is now an alternative to prescription drugs that is easier to obtain and more powerful. Illicit fentanyl is now the preferred opioid and the PDMPs have absolutely no effect on its rapid rise. I would not be surprised if prescription opioid deaths start to fall, not due to the effectiveness of the PDMPs, but due to market competition from illicit fentanyl.”

If PDMP's were effective, Lilly says states that have them would see a decline in opioid overdoses. But in 2016, West Virginia had the highest opioid death rate in country -- over three times higher than Missouri's -- which ranked 25th.

Missouri’s Governor ordered the creation of a statewide PDMP last year, but the state legislature has so far resisted efforts to fund it. Critics say it doesn’t give doctors the necessary tools to prevent overprescribing, but allows law enforcement to track and prosecute physicians and pharmacists.  A spokesman for the Missouri State Medical Association called the program a “witch hunt against physicians.”

Research Uncovers Why Some Pain Meds Don’t Work

By Pat Anson, Editor

An international team of researchers may have discovered why some pain medications are inneffective: they target receptors on the surface of nerve cells that have moved out of reach.

Their findings, published in the journal Science Translational Medicine, may lead to the development of a new class of pain medication that is more potent and less prone to side effects than opioids and non-steroidal anti-inflammatory drugs (NSAIDs).

"Opioids and NSAIDs do not work for everyone and have unacceptable side effects, particularly when used over a long period of time," said Nigel Bunnett, PhD, a professor of surgery and pharmacology at Columbia University Medical Center.

"However, previous efforts to develop more effective analgesics have been stalled by our limited understanding of the mechanisms that allow nerves to sense and transmit pain signals."

Many pain medications work by targeting protein receptors on the surface of nerve cells that transmit pain signals. One receptor – known as the neurokinin 1 receptor (NK1R) -- causes pain and inflammation when activated.

In a series of laboratory experiments on rodents, Bunnett and his colleagues discovered that NK1R, when stimulated by pain, quickly moves from the cell surface to inside the cell membrane, where it continues to function outside the reach of pain medication. Researchers found that when they added a lipid (fat molecule) to painkillers that can cross the cell membrane, they effectively blocked NK1R and provided potent and durable pain relief to the rodents.

"From these experiments, we have demonstrated that designing NK1R inhibitors that are capable of reaching the endosomal network within nerve cells may provide much longer-lasting pain relief than currently available analgesics," said Bunnett. "We think that modification of many existing compounds, as we did with NK1R inhibitors, may have the potential to enhance the effectiveness of many different classes of medications."

The next step for researchers is to see if the same results can be found in humans. If proven, it could mean that current pain medications could be redesigned to make them more effective.

"This is a proof-of-concept study that shows that we can re-engineer current pain drugs and make them more effective. The challenge is now to translate the technology into human clinical trials. This is a complex and challenging path – but the ultimate benefits to patients with nerve pain are potentially highly significant," said Dr. Meritxell Canals of Monash Institute of Pharmaceutical Sciences at Monash University in Australia.

The study was supported by grants from Australia’s National Health and Medical Research Council, the Australian Research Council, and Takeda Pharmaceuticals.