New York Times Pulitzer Prize-winning columnist Maureen Dowd recently traveled to Denver to report on recreational marijuana sales in Colorado. She bought a THC-infused candy bar that looked, she said, like the Sky Bars she loved as a child.
When a nibble failed to produce a response after a short period of time, she ate some more. This was, it turned out, a significant miscalculation.
Her column, headlined “Don't Harsh Our Mellow, Dude,” described what happened next: “For an hour, I felt nothing. I figured I'd order dinner from room service and return to my more mundane drugs of choice, chardonnay and mediocre movies-on-demand.
“But then I felt a scary shudder go through my body and brain. I barely made it from the desk to the bed, where I lay curled up in a hallucinatory state for the next eight hours. I was thirsty but couldn't move to get water. Or even turn off the lights. I was panting and paranoid, sure that when the room-service waiter knocked and I didn't answer, he'd call the police and have me arrested for being unable to handle my candy.”
Ms. Dowd clearly could have used a refresher course in cannabis pharmacokinetics to manage her mellow. This knowledge is important not only for marijuana tourists but also for primary and emergency physicians who will have to counsel and treat patients who, like Ms. Dowd, let their enthusiasm and ignorance get the better of them. As a public service, here are four things to know about the toxicology of cannabis:
The pharmacokinetics of marijuana is completely different when ingested than smoked. The effects of smoking marijuana occur quite rapidly, generally within seconds or minutes. Peak effects occur within 15-30 minutes. The short onset and time to peak effect make it relatively easy to titrate the dose and avoid the couchlock Ms. Dowd experienced.
When marijuana (or THC) is ingested, the onset, time to peak effect, and duration are not only markedly prolonged but also extremely variable, depending on dose, body habitus, time of last meal, and medications, among other factors. Onset of psychotropic effects after ingestion of THC is delayed for 30-90 minutes, with peak effect occurring at one to two hours. (Peak effect was as late as four to six hours after ingestion in some studies.) The high can last for four to 12 hours, and this extended time can make it difficult for an inexperienced user to titrate his consumption. (An excellent reference covering these issues is Clin Pharmacokinet 2003;42:327.)
THC has an active metabolite. Δ9-tetrahydrocannabinol (THC) is the primary psychotropic compound in marijuana. THC goes directly to the brain when marijuana is inhaled, and produces almost immediate effects.
Ingested marijuana, however, is subjected to first-pass metabolism in the liver, where cytochrome P450 enzymes convert some THC to 11-hydroxy-THC, an active metabolite that might be even more psychotropic and longer lasting than THC itself. The time it takes for THC to be absorbed from the gastrointestinal tract, pass through the liver, and be converted to the active metabolite explains why the pharmacokinetics of ingested cannabis is prolonged.
Pure THC in edible products has effects significantly different from unprocessed marijuana. Marijuana itself contains a number of cannabinoids that act together to produce the high. THC is responsible for the euphoria as well as the paranoia and panic. THC can also cause psychotic behavior in some. Cannabidiol, another major component of marijuana, alleviates anxiety. Edible products are infused with almost pure THC, so the effects they produce can be surprisingly strong and extremely frightening if the dose is not controlled. Even those accustomed to smoking marijuana can easily ingest more than they intended and experience an alarmingly bad trip.
THC dosing of edible marijuana in Colorado is insane. Richard Zane, MD, the chairman of emergency medicine at the University of Colorado Medical Center in Denver, said on the National Public Radio talk show On Point that the amount of THC in some marijuana edibles is completely irrational. The usual recommended moderate starting dose is approximately 10 mg THC, and some cookies can contain six doses and some lollipops as many as 10. Dr. Zane said the university's ED sees out-of-state marijuana tourists every day who present with bad reactions to THC, such as agitation, unremitting violent vomiting, hallucinations, and psychosis.
Even if one doesn't live in Colorado, it is important to be familiar with these issues. As of this writing, 23 states and the District of Columbia have legalized medical marijuana. Patients will need to be counseled on dosing, effects, and implications for driving. Pharmacokinetics has never been so important.
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