Medical marijuana doesn’t cause users to get high, except when it does.

Such is the complexity of what is a diverse and divisive substance — outlawed by the federal government but approved in 33 states and the District of Columbia as a multi-purpose medication that’s gaining momentum for legal adult recreational use.

Marijuana comes from the cannabis plant. The prominent cannabis plants are cannabis indica and cannabis sativa. Cannabis consists of hundreds of chemical entities and dozens of chemical compounds. Its most well-known compounds, when activated by heat, are THC and CBD.

THC, or delta-9-tetrahydrocannabinol, produces psychoactive effects in users. Simply put, it’s what makes users high. CBD, or cannabidiol, is not psychoactive and doesn’t mimic that same feeling of intoxication. Sativa strains are generally heavier in THC while indica strains have higher CBD content.

The human body’s endocannabinoid system naturally produces compounds similar to that of the cannabis plant, according to Dr. Kent Vrana, chair of the Department of Pharmacology at Penn State College of Medicine, Hershey. The system’s receptors interact with the cannabinoids, or compounds, from marijuana when it’s ingested, he said.

“Drugs we’ve developed, especially drugs of abuse (like opioids), always worked through something we already have,” said Vrana, one of the certified researchers in the Pennsylvania medical marijuana program.

“Marijuana compounds are no different than that,” Vrana said.

Forms, effects vary

Pennsylvania’s medical marijuana program allows for specific forms of product: pill, oil, tincture, liquid, topical, dry leaf and concentrates for vaporizers and nebulizers. Varied forms allow for varied administration. A tincture is dropped under the tongue. A pill is swallowed and a topical cream is rubbed into the skin. Oils and leaf can be used to create edibles and teas.

Pennsylvania law makes one thing clear: Smoking medical marijuana in joints, pipes, blunts, bongs and the like is illegal. Another clear aspect: no one but certified patients can legally use marijuana.

Simply smoking marijuana from a medical aspect doesn’t allow for regulated control of the compound ingested, particularly THC, Vrana said. Heavy puffing or light puffing, Vrana said it can’t be known how much THC is being taken in without patient-specific monitoring.

The balance of THC and CBD in each product varies. Some contain high amounts of THC and low amounts of CBD, or vice versa, meaning some — but not all — medical marijuana can cause a user to feel high.

“Some have very, very trace amounts of THC in them and have no psychoactive effect,” said April Hutcheson, communications director, state Department of Health.

A patient’s diagnosed condition would largely determine the product and initial dosage recommended by a practitioner or the in-house pharmacist at each medical marijuana dispensary, according to Hutcheson. She added that the dosage is adjusted as needed.

“The intent of (medical) marijuana isn’t to intoxicate you when you’re using it for help,” said Dr. Thomas Trojian, the director of the sports medicine fellowship at Drexel University College of Medicine. “It’s supposed to be used in low doses and not be an intoxicant. Recreationally, people use it for joy. The dosage that people recommend for ailments aren’t to make one high. It’s just enough of a dose to help with different aspects.”

The CBD for sale over the counter in convenience stores is extracted from hemp, not marijuana. It’s not regulated and not a part of the state medical marijuana program.

‘Making it more tolerable’

Dr. Brooke Worster of Thomas Jefferson University Hospital, Philadelphia, a certified physician for the state’s program, specializes in cancer pain management. She said she’s certified more than 500 patients for medical marijuana use.

Cannabis can affect one’s perception of anxiety, ease nausea and vomiting and stimulate hunger, the latter effects being particularly beneficial for cancer patients undergoing chemotherapy, Worster said. It also alters one’s perception of pain, she said.

“It’s modulating how you’re perceiving pain. It’s not actually changing the pain. Hopefully, it’s making it more tolerable,” Worster said.

“It’s true, marijuana gives you the munchies,” Vrana said.

Marijuana’s continued status as a Schedule I narcotic — classified in the same category as heroin — prevents expansive research. Federal restrictions have begun to ease ever so slightly, though not as quickly as research advocates prefer. Pennsylvania took a novel step in adopting a clinical research initiative within its own program that could yield many discoveries in medical use.

Pennsylvania’s program is restricted to certified patients and caregivers. They’re only eligible on referral by practitioners registered with the program. Access to dispensaries is restricted to patients with a state-issued card.

Production of the product patients use is controlled and monitored by the state from seed to dispensary shelf. The state knows the water source and pesticide types used at the growing facility, according to Hutcheson. The plant is tested when it’s harvested and tested again when it’s formed into a final product, she said. When the medication is dispensed, patient and dosing information is input into a centralized monitoring system. Hutcheson said a 30-day supply per product is the limit.

Importance of research

Cannabis remains little understood by the public and even by physicians controlling access to the state’s medical program.

Pennsylvania’s inclusion of a clinical research initiative within its medical marijuana program is a unique feature among the states allowing medical use. Researchers like Vrana, Worster and others at eight state medical colleges will explore cannabis’s properties toward reinforcing current medical uses, mitigating risk to patients and discovering new potential health benefits.

Research is necessary on medicine with so many outstanding questions, Vrana and Worster agreed.

“It’s kind of crazy,” Worster said. “I can’t tell you exactly the right dose or strength you need.”

The Wolf Administration announced in early September it seeks applications to approve three clinical registrants to grow, process and dispense medical marijuana for researchers and their subjects. Once these operations are running, hands-on studies can begin.

The work Vrana will lead within the state program will study animal models of pain, seeking to determine specific dosage amounts of THC and CBD, he said. Test strains of the medicine won’t be dispensed to human patients, Vrana said. Irritable bowel syndrome, one of the existing 23 qualifying conditions, are among the maladies that will be studied, he said.

“We here at the commonwealth are at the forefront of the research of medical marijuana,” Vrana said. “I’ve done some good work. I’ve never done any work that’s had this kind of public interest.”

Food and Drug Administration limits on research rule out controlled trials. Research patients can use medical marijuana they’re receiving within the program but researchers can’t control their doses and potency of medication, Worster said. There are no blinded placebo controls, too, she added.

Worster said such research is limited to observational study: Monitoring a patient’s condition and how the medical marijuana product they’re choosing to consume is impacting their health.

However, Worster said “there’s no guessing” that medical marijuana is safer than other medicines she prescribes, such as opioids.

“I don’t think it’s for everyone. It’s certainly not the magic bullet or without some risk,” Worster said.

“I will tell you I think it is incredible the medical community hasn’t stepped up more than it has because patients are pushing for it. People are saying, ‘I’m using it and it’s helpful. Not one or two but millions of people.”