It is challenging to hit clinical goals for pain treatment, and few investigational non-opioids have shown to be as effective as opioid options. New, less-addictive pain drug approvals have remained elusive. Volkow said even new medicines could have the potential for addiction — and that regulators would have to make sure there are strong safeguards about how, where and when the drugs could be used to avoid another crisis of overprescribing, addiction and misuse.
The NIH HEAL Initiative, a public-private effort launched in 2018 to tackle the opioid crisis, has also spurred more research into nonaddictive pain treatment. But a new option driven by this funding will likely take more than a decade to come to market because most molecules are not yet in human clinical trials. Volkow said the soonest new pain drugs could be in the later-stage trials needed for FDA approval is about five years.
The NIDA director said the agency has been working with FDA, NIH and industry partners “to figure out ways that can accelerate the process of bringing analgesic products that are safer and effective.”
An influx of NIH funding from Congress has also sparked initiatives to build two networks, one of which should help speed up recruitment of patients for clinical trials and another that should help speed up other basic science work such as toxicity studies, she added.
Volkow acknowledged that a concerted effort will be needed to track the addictive potential of new pain drugs. The prescription painkillers that have fueled the current addiction crisis were thought to be relatively low-risk for addiction based on earlier short-term studies. Those studies turned out to vastly understate the risks.
But Volkow said society can’t dismiss a medicine because it carries risks of addiction. The task is to manage that risk in ways that keep patients safe.
If a pain medicine has addictive potential, regulatory processes should be put in place to tightly control access, she said. For example, ketamine is highly addictive but is being investigated for treating depression and pain. To mitigate risk, ketamine is being delivered in highly regulated and controlled settings, such as through injections given by a physician.
Fentanyl is another drug that can be very safe when used in hospitals, often administered by an anesthesiologist. But fentanyl has caused much harm when administered in outpatient settings, and it’s been lethal when mixed with street drugs.
Volkow said the health care systems need to better adapt to these drugs.
“I’m a little concerned about delivery systems that will enable the use of [addictive] drugs outside” of controlled settings, she said. This could open up a “Pandora’s box to allow a drug that could be diverted and abused.”
She also emphasized the importance of FDA requiring long-term studies of pain medicine, even if those are conducted following marketing approval.
Cannabis compounds could also prove to be an alternative, said Volkow. Both THC and cannabidiol, a component of the plant that does not give a “high” like THC, are being explored as pain and even addiction treatment, though research is still early — and federal restrictions on the plant make it difficult to study.
“We need to know adverse or positive effects, but it’s been difficult to do research because of the Schedule 1 process,” Volkow said, referring to the restricted drug classification that comes with a host of barriers to buy, store and research the drug. She said NIDA is working with DEA and FDA for solutions “that will not make research on marijuana so cumbersome.”
In the meantime, her institute is concerned about climbing cannabis rates as well, especially among teen girls. The latest Monitoring the Future study, released in December, showed a significant uptick in cannabis use and especially vaping among that population and teens as a whole.