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Large study finds canna-moms’ kids have normal brains

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A recent large-scale longitudinal study has found no ties between cannabis use during pregnancy and different neurodevelopmental outcomes for exposed children. The study, released in June in the journal Paediatric and Perinatal Epidemiology, had more extensive controls for confounding factors than in previous studies, and followed children to age 20. When researchers accounted for the characteristics of the parents, researchers found no associations between prenatal cannabis and neurodevelopmental differences.

This is positive news, given the fact that 4.2% of pregnant women report using cannabis, and the number has been increasing. Pregnant cannabis users also face arrest, prison, and removal of children in multiple states.

Prenatal marijuana exposure was not associated with secondary outcomes or risks of clinical deficit in any neuropsychological assessments.

Oliver G Isik, ‘Neurodevelopmental outcomes in children after prenatal marijuana exposure,’ 2023

Is cannabis safe during pregnancy?

(Leafly)

Cannabis use during pregnancy is still a highly controversial issue. Some praise the plant’s ability to ease morning sickness and the aches and pains of pregnancy. Others worry that cannabis’ potent blend of chemicals may negatively impact the developing child. Unfortunately, research on the topic has been fairly inconsistent. 

Some studies show heightened neurodevelopmental differences, such as ADHD, anxiety, and autism, in children who were exposed to cannabis in utero. Others find no association.

Low participant numbers, or weak observational study designs can make it difficult to tell whether cannabis is actually causing these differences.

For example, a 2020 systematic review found that cannabis use during pregnancy may be associated with ADHD and affective symptoms like anxiety in the resulting children. Another 2020 study found that children whose mothers used cannabis while pregnant were 50% more likely to receive an autism diagnosis. 

But these studies may not hold up to scrutiny. Experts point to issues in the methodology of much of the available research. Low participant numbers, or weak observational study designs can make it difficult to tell whether cannabis is actually causing these differences. 

Neurodivergent children: Cannabis or parental factors? 

One of the major issues confusing the research is whether parental characteristics, such as other drugs use or preexisting medical conditions, are being taken into account. For instance, a 2021 study found no association between autism and prenatal cannabis use when maternal education, and alcohol and tobacco use was considered. 

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A 2023 study found that when maternal stress (a known risk factor for both autism in offspring and cannabis use) was factored in, cannabis exposed children had no higher risks of autism. And a study in 2021 on 2408 children found similar results for ADHD. When confounding factors were considered, no associations remained. 

Related

We spoke to the author of that new study on prenatal cannabis exposure

Recent estimates suggest the heritability of autism—the extent to which autism is passed on from parents to children—may be as high as 90%. For ADHD it can be as high as 88%. If researchers aren’t considering whether parents have traits associated with these conditions, it can introduce serious bias into the study. 

This is especially important given the fact that both autism and ADHD are correlated with higher levels of substance use, and cannabis may relieve symptoms for both. It may seem like cannabis is causing neurodevelopmental differences. But it may be that parents who are more likely to pass on these differences on, are also more likely to use cannabis during pregnancy. 

Study finds cannabis not associated with neurodevelopmental differences

The study released this month, from researchers at Columbia University and the University of Western Australia, Perth, was a step above most of the research on this topic. They opted to control for a wide range of clinical and sociodemographic parental characteristics, which helps avoid many of the limitations previous studies have had. Their study also took place over a long period of time. Using data on 2,868 children from the Raine Study, researchers were able to analyze the progression of prenatal cannabis exposure from pregnancy to age 20.

This is a much longer span of time than most studies have looked at.

To accomplish this, the children underwent neuropsychological testing at ages 10, and again at 19 or 20. This is a much longer span of time than most studies have looked at. Combined with a large sample size, and more extensive controls, it provides a clearer picture of what can really be attributed to prenatal cannabis use. 

With these controls in place, researchers found no associations. The authors explain that “Children with PME [prenatal marijuana exposure] did not perform worse on neuropsychological assessments than unexposed children at ages 10 and [again at ages] 19 to 20.” 

Related

Consuming Cannabis During Pregnancy: Here’s What the Science Says

Study limitations: Cannabis keeps changing

While this is positive news, the study was not without its own limitations. One major factor is the shift in cannabis potency and differences in how people use cannabis, over the last few decades. This cohort included children born from 1989-1992, and may reflect lower levels of THC exposure than would be encountered in children born today. The study’s authors conclude that “further research is warranted in a more contemporary birth cohort with a range of neuropsychological outcomes to further elucidate the effect of prenatal marijuana exposure on neurodevelopment.” 

Until we get more conclusive data, experts still recommend that women abstain from cannabis use during pregnancy.



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Can lemon-smelling weed cause less anxiety than others?

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Top study takeaways:

  • Ever eat mangos to help you get higher? Maybe pound some lemonade to prevent anxiety
  • Test subjects who vaped lots of the terpene limonene with their weed reported lower anxiety in a small study

Leafly Ph.D Nick Jikomes dissects the hype new study on the smell molecule limonene below. Report your findings in the comments section.

The “entourage effect” is the idea that the psychoactive effects of cannabis result from a combination of different plant molecules. The idea is widely used in the cannabis industry to help explain the distinct effects that cannabis strains are reported to have–each one contains a different combination of THC, terpenes, and other compounds. These claims have been largely theoretical, with limited empirical evidence to show that specific combinations of cannabinoids and terpenes reliably induce measurably different effects in humans.

A new study, however, investigates whether the common cannabis terpene limonene, when consumed together with THC, results in different effects compared to THC on its own.

A bit of limonene is in many weed varieties

Limonene is one of the most abundant terpenes found in commercial cannabis. Cannabis strains with the highest limonene levels typically contain between 1 to 3% limonene by weight. Commercial THC-dominant cannabis flower today often has THC content in the 20-25% range, meaning that the most limonene-rich strains will have a roughly 20:1 ratio of THC to limonene. 

Limonene is found naturally in many citrus fruits. On its own, it has a pleasant, citrus aroma. A limited number of animal studies have observed anti-anxiety effects in rodents given limonene. Similar observations have been made in human studies, although they had small sample sizes or lacked important controls. Given that anxiety is a common side effect of THC—especially when relatively large doses are consumed—it has been hypothesized that limonene may be able to mitigate these effects. If true, this would suggest the possibility that THC-dominant strains high in limonene might be less likely to elicit anxiety than those with lower limonene content. 

Vaping limonene and THC—for science!

A robust terpene profile in weed adds to the flavour and overall experience. (MysteryShot/Adobe Stock)
(MysteryShot/Adobe Stock)

In this new study, researchers at Johns Hopkins administered different combinations of THC, limonene, and a placebo of distilled water to twenty human subjects in a double-blind trial. Each person participated in several separate vape sessions where they received one of the following:

  • Limonene alone (1mg or 5mg)
  • THC alone (15 mg or 30 mg)
  • THC + limonene together (15 or 30 mg THC + 1 mg limonene)
  • THC + limonene together (15 or 30 mg THC + 5 mg limonene)
  • THC + limonene together (30 mg THC + 15 mg limonene)
  • Placebo (distilled water)

The subjects were healthy adults who used cannabis intermittently. A hand-held Might Medic vaporizer (made by Storz and Bickel) was used for administration. Subjects consumed 15 and 30 mg doses of THC because, based on previous research, those doses often trigger small (15 mg THC) to moderate/large (30 mg THC) psychoactive effects, with the larger dose expected to trigger more side effects like anxiety. Researchers assessed participants using standardized questionnaires. One of these, the “Drug Effect Questionnaire,” asks subjects to rate various subjective drug effects on a 0-100 scale. Another, the “State-Trait Anxiety Inventory (STAI-S),” assessed their anxiety/distress levels before and after drug administration. Researchers also tracked heart rate, blood pressure, and plasma levels of THC and limonene. (For more details on the study methods, including the standardized procedures, check out the paper itself.)

What did they find? Did the presence of limonene affect the subjective effects of THC, or reduce side effects like anxiety and paranoia?

Three limonene-dominant hype strains

A photo of Connected Gelonade — Lemon Tree and Gelato. (David Downs/Leafly)
Gelonade. (David Downs/Leafly)

And the results come in

I recently spoke with the lead author of the study, Dr. Ryan Vandrey of Johns Hopkins University, about how his team designed the study and built in important controls. For one: test subjects received the real deal molecules, not some burned-up version.

“We made sure that when we heated it at this temperature, this device, we didn’t convert these things into something else,” Dr. Vandrey explained. “So we were very careful to get our dosing methods secure, and to work with this. We opted for inhalation and vaporization in particular, so we know that our doses are being delivered fully and completely.”

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Consumption of THC went as planned. The control placebo containing 0 mg THC did not cause substantial subjective effects, anxiety or paranoia, or changes in heart rate. Consumption of 15 or 30 mg of THC did trigger these changes, with the higher dose producing larger effects on average.

“We picked two doses of THC, 15 milligrams and 30 milligrams, which to the occasional cannabis user will get people moderately high at pretty dang high,”

Dr. Ryan Vandrey, Johns Hopkins University

Related

How to order weed delivery online with Leafly

But did consumption of limonene together with THC lead to different effects compared to the same dose of THC alone? Yes—if you’re limonene-maxing.

When limonene was administered alone, without THC, its effects did not differ compared to the placebo.

But with co-administration of THC and limonene, however, the team saw differences compared to THC alone, but only at the highest dose of limonene (15 mg).

Compared to 30 mg of THC alone, consumption of 30 mg THC + 15 mg limonene resulted in lower subjective ratings for “anxious,” “paranoid,” and “unpleasant drug effect.”

Subjective ratings of “anxious” and “paranoid” were less than half of those seen with 0 mg limonene.

Subjective ratings of “anxious” and “paranoid” were less than half of those seen with 0 mg limonene.

Although the result was statistically significant at the highest limonene dose (20 mg), the sample size (n=20) was small and it’s not clear if most subjects saw this effect, or a small minority experienced large differences.

The presence of limonene did not influence physiological measures like heart rate, nor did it lead to differences in the intensity of THC’s subjective effects or blood levels of THC.

“That’s important… because it suggests that limonene isn’t somehow interfering with THC absorption. It’s not somehow changing the pharmacology. It’s not blocking THC’s ability to bind to the cannabinoid receptor,” Dr. Vandrey told me.

Did test subjects detect any lemon?

image-of-cannabis-judge-smelling-weed
(AdobeStock)

Because limonene has a taste, smell, and influences vapor quality, blinding may have been an issue, especially at higher doses of limonene.

Put another way, if subjects could taste or smell this terpene, or noticed that the vapor felt different, it could have colored their experience.

According to Dr. Vandrey, however, the team’s drug delivery design minimized the subjects’ ability to discern what they were consuming via taste or sight.

“We did everything to maintain the blind in this study,” he said. “The drugs were sealed inside of the vaporizer, but they couldn’t see it, they couldn’t smell it or anything like that.”

Weed’s entourage effects remain hard to pin down

While the results of Vandrey’s study proved statistically significant, the size of the effect was quite modest. Co-administering THC with 15 mg of limonene resulted in decreases of anxiety, but not 1 mg or 5 mg of limonene.

It’s important to note a key caveat: Subjects were not consuming whole-plant cannabis products like those we can buy in dispensaries. They were only consuming specific combinations of THC and/or limonene.

The modest effects they saw were only seen with 30 mg of THC with 15 mg limonene, which is a 2:1 THC:limonene ratio. This is not a combination found in commercial cannabis flower. Expect a roughly 20:1 THC:limonene ratio for even the most limonene-rich strains.

Taken at face value, the results of the Johns Hopkins study indicates maxing out on limonene may reduce The Fear.

However, they do not demonstrate that limonene-rich, THC-dominant cannabis purchased from a dispensary contains enough limonene to accomplish the same goal.

If limonene or other cannabis terpenes can indeed reliably modulate the effects of THC in commercially-available cannabis products, future research will have to focus on them. Such products contain more complex mixtures of THC and a variety of terpenes and other molecules, many of which are present at low levels. Does the “entourage effect” really explain all the effects of weed? Researchers will need to carefully measure the effects of real-world stuff to know for sure.

For more detail on this study, listen to my full conversation with Dr. Ryan Vandrey. Mind & Matter is a science column by Nick Jikomes, PhD focuses on how psychoactive drugs influence the mind & body. It is inspired by the long-form science podcast, Mind & Matter.

What do limonene strains do to you? Sound off in the comments below.



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“A big deal”: What the feds’ move to reclassify marijuana means for Colorado cannabis

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Cannabis advocates in Colorado cheered the Biden Administration’s reported move to reclassify marijuana and said the decision likely would reduce businesses’ tax burden significantly.

Industry leaders cautioned that such a move — if finalized — would not resolve some major challenges facing the industry, such as limited access to banking. But they pointed to the symbolic importance of preparations by the U.S. Drug Enforcement Administration to downgrade the substance’s drug classification.

A man pours cannabis into rolling papers as he prepares to roll a joint the Mile High 420 Festival in Civic Center Park in Denver, April 20, 2024. (Photo by Kevin Mohatt/Special to The Denver Post)

Read the rest of this story on DenverPost.com.



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Study: Cannabis can make workouts more fun, but it’s no performance-enhancer

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The study of 42 runners, published Dec. 26 in the journal Sports Medicine, comes almost exactly 10 years after Colorado became the first state to commence legal sales of recreational marijuana, at a time when cannabis-users increasingly report mixing it with workouts. “The bottom-line finding is that cannabis before exercise seems to increase positive mood and enjoyment during exercise, whether you use THC or CBD. But THC products specifically may make exercise feel more effortful,” said first author Laurel Gibson, a research fellow with CU’s Center for Health and Addiction: Neuroscience, Genes and Environment (CU Change).

https://www.colorado.edu/today/2024/01/03/study-cannabis-can-make-workouts-more-fun-its-no-performance-enhancer



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