There are hundreds of strains of marijuana — each containing hundreds of different chemicals — but only one molecule makes much difference, scientists say.
It's all about the THC.
Purveyors and boosters of marijuana — or cannabis — whether recreational or medicinal, counterclaim that the experience varies to great effect among all the amazing varieties cultivated over thousands of years.
Almost five millennia after the Chinese used medicinal cannabis, Colorado voters approved it in 2000, and they did the same for adult recreational use in 2012. A majority of the state's voters have decreed cannabis is good medicine and good fun, but they might not know what the drug is doing to the body.
When a person smokes, inhales or ingests marijuana or pot — the green, brown or grayish dried and shredded leaves, stems, flowering buds or seeds of plants called cannabis sativa or cannabis indica — more than 200 different chemical compounds course through the body. About 60 of them are called cannabinoids.
“Everybody likes something different,” said Ean Seeb, co-owner of the Denver Relief Medical Marijuana Dispensary. “They can now pick what really works for them.”
Yet after some 75 years of scientific research, it has been found the concentration of the psychoactive compound, THC, is what really matters, said psychopharmacologist Kari Franson, an associate dean and professor with the University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences.
Franson worked at an institute that studied the effects of cannabinoids in healthy volunteers in the Netherlands, where it was easier to do research on it than in the U.S.
“You can study, study, study it, but it's THC (Delta-9-tetrahydrocannabinol) — that is the active ingredient,” Franson said. “And there are certain things that happen to everyone who takes THC.”
These, she said, are a feeling of pleasure or high, motor instability, decreased reaction time, attention deficit and increased heart rate.
“People think it mellows them out, but it causes an average increase in heart rate of 16 beats per minute,” Franson said. “That's why people who take high doses they are unaccustomed to can experience significant anxiety or paranoia.”
Other THC effects commonly experienced are increased appetite, decreased nausea, decreased motivation and decreased pain perception.
Additional typical effects are bloodshot eyes, decreased pressure inside the eye (it's used to treat glaucoma), heightened sensory perception (intense colors and sounds), distorted sense of time and sometimes a dry mouth.
Some effects are felt as soon as THC enters the bloodstream — much more quickly if inhaled. Delivery is key — joint, blunt, water pipe or a volcano (in which vapor only is collected in an expandable bag). Effects typically last an hour to a few hours, but the fat-soluble chemicals stay in the body for much longer.
Absorption of ingested THC is much slower.
After the high is over, some users feel sleepy or depressed.
Whatever is happening, Franson said, it's THC that's doing it.
“I think it all has to do with dose. The rest is marketing,” Franson said. “It's folklore.”
Users beg to differ.
Seeb and many others say the two main types of cannabis, sativa and indica, produce very different effects. Marijuana strains range from pure sativas to pure indicas, but most are combinations or hybrids after thousands of years of cropping and recropping, he said.
Indica, nicknamed “in da couch,” provides a deep feeling of relaxation or sleepiness compared with sativa, “viva sativa,” which provides a more energetic or uplifting high, Seeb said.
Other users have strong preferences for different tastes and smells, which contribute to the subjective experience of pleasure.
“There are really pronounced differences across thousands of strains,” Seeb said. “Some smell very sweet, like oranges or grape Kool-Aid. Some people like the stinkiest cannabis they can find. It can smell like skunk, diesel fuel (Bio-Diesel) or a dirty diaper (Sour Diesel). Gumbo is a delicious, sweet and spicy indica strain with beautiful floral hints, but also strong and pungent.”
Seeb, who suffered a traumatic skiing accident that left him with chronic muscle spasms in one arm, said he is a big fan of Ultimate '91 ChemDawg. It helps him relax his muscles and fall asleep after long workdays of 16 to 18 hours. No motivation problems here.
“I can't make any claim one strain will have any one effect on everybody,” Seeb said. “What makes one person giggle will make someone else paranoid.”
For those who abstain and wonder about whether making their way through a haze of marijuana smoke can get them high, Franson says not to worry.
“It takes an absurd amount of marijuana secondhand smoke to cause a positive test in a nonsmoker,” Franson said.
A test 20 years ago showed that it required the smoke of 14 marijuana cigarettes in an unventilated 10-foot-square room before a nonsmoker had detectable amounts in his system.
“That's pretty smoky,” Franson said.
Most of THC's activity is in the brain and central nervous system, although there are receptors located in the heart and other cells, such as the body's inflammatory-response cells.
Human bodies naturally manufacture chemicals similar to THC, which is why it works on us, Franson said. It hijacks receptors in the brain used by natural chemicals called neurotransmitters, specifically endogenous cannabinoids. One of them, anandamide, has been identified as regulating mood, memory, appetite, pain, learning and understanding.
These receptors are all over the brain — including the basal ganglia (which affects involuntary muscle movements), the hippocampus (used in short-term memory) and the cerebellum (which controls motor coordination).
“The cannabinoid receptor system is one of the biggest systems. Your brain is chock-full of them,” said Dr. Christian Hopfer, an associate professor of psychiatry at University of Colorado Hospital's Center for Dependency, Addiction and Recovery.
“You need (the body's natural cannabinoids), and it has an effect when you're messing with those receptors,” Hopfer said.
THC mimics the body's cannabinoids. Both interact with the same receptors. When THC binds to the receptor, it interferes with normal brain function, such as dopamine regulation.
Dopamine is part of the body's natural reward system and a key molecule in many brain functions, such as attentiveness, motivation, learning, memorization and motor control. THC increases dopamine in the short term, but ultimately interferes with the body's own reward circuit.
One of the body's own cannabinoids' purposes is to decrease the excitability of brain cells, or neurons, activated by adrenaline (or norepinephrine) in a fight-or-flight response to a perceived threat.
“But we eventually have to turn off this response or the neuron dies,” Franson said.
That's the job of the body's cannabinoids. But they jump on and jump off receptors much faster than THC, Franson said. The body's cannabinoids don't create a high.
“But THC jumps on and stays there,” she said. “It has a prolonged and pronounced effect.”
With chronic cannabis consumption, the body decreases the number of receptors for its cannabinoids. Researchers have found that this results in reduced blood flow — and glucose and oxygen — to the brain. This could manifest as attention-deficit, memory loss and other impaired mental abilities.
“There is evidence you don't recover all your mental capacity when you quit using,” said Hopfer, who treats marijuana and other addictions. “It's a very insidious addiction. It's very hard to treat. Its effects are subtle, gradual and less dramatic. And it's been trivialized.”
He said he thinks the media overall has been pro-marijuana in its coverage of legalization.
“People shouldn't assume they know this drug based on Cheech and Chong movies,” Franson said.
Marijuana continues to be listed by the U.S. Food and Drug Administration as a Schedule I drug — high potential for abuse and no currently accepted medical use — along with opiates and derivatives (heroin), stimulants (methamphetamine) and hallucinogenics (LSD) and depressants (methaqualone).
“There's something crazy about the feds labeling cannabis Schedule I and states legalizing it,” Hopfer said. “It strikes me as a bad way of doing public policy. The truth is we don't really know that much about marijuana. We need to sort it out. But we have declared it a medicine by popular vote. It's a bad system. Now the popular view here is that it should be regulated like tobacco.”
When cannabis is smoked like a cigarette, the smoker's lungs take in a horde of chemicals and particulates.
“Do I know that direct contact of these compounds doesn't harm the lungs. I don't know that. And nobody knows that,” Franson said.
Cannabis boosters and detractors offer conflicting evidence of whether it prevents or causes cancer, or does both.
“We just don't have full understanding,” Franson said. “I think we ought to know what this stuff does before we (broadly) use it as medicine.”
Her main complaint about cannabis as medicine is that it's not “pharmacological,” by which she means you can't administer a consistent dose and predict a consistent response.
Nevertheless, she acknowledges cannabis is being used successfully to alleviate pain, lessen the bad side effects of chemotherapy and prevent blindness from glaucoma.
And, with much less scientific evidence behind it, it is also used to treat epileptic seizures, stop the spread of cancer (with a chemical called cannibidiol, not THC), slow the progression of Alzheimer's disease and more. Franson said these claims are not well-supported.
Where cannabis is concerned, however, many voters and users are willing to rely on anecdotal evidence and personal experience — and are just trying it out as a cure for an increasing number of ailments.
“We have such a wide variety of patients who come,” Seeb said. “We're really starting to see the plant is a miracle plant that heals many things.”
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