At a Paul McCartney concert at San Francisco’s AT&T Park in 2010, Matthew Springer, PhD, wasn’t shocked to be surrounded by marijuana smoke.
He was, however, amazed that the audience tolerated it without complaint.
“All of these people knew to avoid cigarette smoke,” recalls Springer, a professor of medicine at UCSF. But, “we haven’t been given that [public health] message about marijuana smoke, so people thought that it was somehow okay.”
Was it? Springer wondered.
Now that recreational, in addition to medical, marijuana is legal in California there is renewed urgency to understand the drug’s health effects, both positive and negative.
Scientists recognize marijuana’s contradictory status: the drug has significant proven and potential therapeutic uses, but it can also lead to tremendous public health problems. Everyone agrees that a stronger evidence base is key.
“We are left with so many questions,” says Reto Auer, MD, MAS ’13, who launched a study on marijuana and cognitive function while at UCSF. Published in JAMA Internal Medicine in 2016, it showed that self-reported “long-term marijuana users” experienced some memory problems by midlife.
The Feds: just say ‘no’ to research
Marijuana, now legal by a doctor’s order in 29 states and recreationally in eight states (plus the District of Columbia), remains in the same class federally as heroin – a Schedule I drug, designated as having “a high potential for abuse” and “no currently accepted medical use.”
Federally, marijuana is considered more dangerous than prescription opioids like OxyContin and Vicodin, which were linked to 15,000 deaths in 2015 and responsible for epidemic levels of addiction and abuse.
Every day, I see patients who benefit from using cannabis as medicine.
“Every day, I see patients who benefit from using cannabis as medicine,” says Donald Abrams, MD, chief of the Hematology-Oncology Division at Zuckerberg San Francisco General Hospital. “It’s a benign and safe agent that’s been used for thousands of years.”
Studying marijuana means navigating complex regulatory hoops, including reviews by the Food and Drug Administration (FDA), the Drug Enforcement Administration (DEA), and the National Institute on Drug Abuse (NIDA).
Included in the DEA’s stringent regulations for purchasing, storing, documenting, and disposing of marijuana is the requirement that each lab must have an alarm-controlled, locked storage container anchored to the floor or wall.
“The DEA visited and determined that we had to do more to bolt down the locked freezer,” says Judith Hellman, MD, vice chair for research in the Department of Anesthesia and Perioperative Care. It took close to a year to get the approvals, says Hellman, who is studying the immune modulating effects of cannabinoids.
Restricted supply: restricted research
The DEA has long designated NIDA as the sole source of cannabis for scientists. Until recently, NIDA, under an exclusive government contract in place since 1968, paid the University of Mississippi to grow all the country’s research-grade marijuana. While production to other growers opened last year, none have yet been able or willing to comply with the agency’s requirements.
But the roadblocks to studying marijuana go beyond the regulatory hurdles. One obstacle, Abrams says, is the limit NIDA puts on the drug varieties used in research. Different marijuana strains have varying chemical components, so they ameliorate clinical symptoms differently.
Cancer-related nausea and poor appetite, for example, are better relieved by cannabis high in THC, marijuana’s psychotropic component. However, there is evidence that chronic pain and inflammation are better relieved by cannabis high in cannabidiol (CBD).
“In the past, NIDA pretty much only had low-THC, zero-CBD strains,” says Abrams. He has long battled with federal agencies to procure cannabis with higher levels of THC and CBD for his research on easing symptoms in patients with sickle cell anemia.
It’s even more difficult for researchers who want to look at newer delivery systems. “Cannabis oil is popular,” Abrams says. But “because the NIDA supply has not yet been trialed in humans, if I [propose] to study it, the FDA will say it’s a ‘novel molecular entity’ and make it difficult to do.”