Groundbreaking study cracks one of pot’s greatest mysteries

cannabis trichomes pot mystery

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A mystery has been lingering over cannabis for nearly as long as people have been smoking pot: Do different types of marijuana get people high in different ways?

California cannabis companies already have an answer to this question, claiming each strain of pot has different terpenes — a type of aromatic compound produced by all plants — and these aromas cause pot to have different effects.

But scientists say there’s almost no scientific basis to support this theory, which has only deepened the mystery. Are strains and terpenes just a stoner fairy tale, or is something actually going on there?

Now, there’s a little science on the stoners’ side.

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This month, researchers at Johns Hopkins University published results from a clinical trial showing that adding a specific terpene to THC changed the experience of getting high. This is the first clinical evidence that terpenes can change the effects of THC.

In the study, participants inhaled two different doses of vaporized THC, either alone or mixed with limonene, a lemony-smelling terpene also found in citrus fruits. While 30 milligrams, the highest dose of THC, caused people to feel anxious and paranoid when inhaled alone, adding the highest dose of limonene significantly reduced these feelings.

Members of the group receiving the highest doses of both compounds were also more likely to report feeling relaxed than any other group, and less likely to find the high dose of THC unpleasant, compared with those who inhaled 30 milligrams of THC alone. The lower doses of limonene did not cause any statistically significant changes in experiences.

Ryan Vandrey, a Johns Hopkins professor and principal investigator for the clinical trial, said the study’s findings could be used to make medical cannabis products more useful by reducing the amount of anxiety caused by THC, one of the negative side effects of using the drug.

“We’ve identified a specific chemical that seems to mitigate some of the risks associated with THC exposure, and that to me is very meaningful,” Vandrey said.

cannabis plant pot mystery
A cannabis cola with visible trichomes and leaves in late flowering stage. Photo: rgbspace / Getty

Vandrey said his team, which included the legendary cannabis scientist Ethan Russo, chose limonene because there was already significant pre-clinical research showing that it has psychoactive effects and because the cannabis industry is already making claims based on the compound.

“If you look in dispensaries and on websites that sell cannabis products, they are specifically claiming that products high in limonene can reduce anxiety and provide a calming, relaxing experience for users,” Vandrey said.

Two research scientists and a medical doctor unaffiliated with the study told SFGATE this latest research is groundbreaking, as it’s the first published clinical trial to test the effects of a terpene in combination with THC. Linda Klumpers, a research assistant professor of pharmacology with the University of Vermont, called the study “successful” and said it shows the combination of THC and limonene “likely gives effects that are different from when the compounds are given alone.”

Klumpers did, however, caution that the study has several limitations and doesn’t prove that terpenes found in natural pot products affect how people experience THC intoxication. The study’s sample size was fairly small — only 12 people — and the inclusion of many different measurements reduced the overall strength of its conclusions, according to Klumpers. The study also did not blind the aroma of limonene, meaning participants could have been aware they were consuming a terpene along with the THC. In addition, the group that reported the strongest effects received doses of limonene higher than anything naturally found in cannabis, limiting its real-world relevance.

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John Streicher, a neuroscience professor at the University of Arizona who has studied cannabis terpenes, said this latest study was a “big step forward” in understanding terpene effects but cautioned that it did not validate the extensive claims already being made by the cannabis industry.

“Unfortunately, this is an area where commercial interests have raced way ahead of the science and are making big claims about what strains and terpenes do what based on no evidence at all. We in the scientific community need to catch up!” Streicher said in an email.

Streicher said he’d like to see a future study comparing different strains of cannabis that contain different levels of terpenes, instead of using purified compounds in isolation.

cannabis flower
Macro detail of cannabis flower ready for harvest with visible trichomes. Photo: rgbspace / Getty

The Hopkins team has filed a patent application for combining limonene and THC to reduce THC-induced anxiety, suggesting the team believes there are possible pharmaceutical uses for its findings. Patents are deeply controversial in the medical cannabis community. Many longtime medical marijuana practitioners and growers worry that pharmaceutical companies will take credit for work done by people who have spent decades working in the shadows with an illegal plant. Vandrey said the patent, if granted, would never stop people from using natural cannabis products.

Whether or not limonene ever finds its way into a pharmaceutical product, the study’s findings are already helping medical doctors who work with cannabis.

Bonni Goldstein, a Los Angeles doctor and a global leader in medical cannabis, said this latest study confirms what she has already seen in her practice: “Terpenes matter” when using medical cannabis.

“I already know that the terpene profile is important when choosing products for my patients, however, having studies like this helps to substantiate what we cannabis practitioners have been witnessing in clinical practice,” Goldstein said in an email.