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Can Cannabis Help With Chronic Pain?

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Chronic pain is the most common reason people turn to medical marijuana. According to a 2019 study, two-thirds of medical cannabis patients in the US listed pain as their qualifying condition.

Thanks to the lifting of cannabis prohibitions and advances in medical research, we now have a solid body of clinical evidence that medical marijuana preparations work for various types of chronic pain. 

Many of those medical studies demonstrate that cannabis is an effective treatment for chronic pain — from cancer, neuropathy, fibromyalgia, multiple sclerosis, arthritismigraine, and others.

That research is welcome news for sufferers for several reasons. Firstly, chronic pain conditions don’t always respond to standard treatment. Secondly, marijuana has less serious side effects than many prescription pain medications, including a much lower risk of addiction and almost zero risk of fatal overdose.

https://cannigma.com/conditions/chronic-pain/?utm_source=The%20Cannigma%20B2B&utm_medium=email&utm_campaign=Newsletter%202.11.23%20%2801HE7QQAAHAQXW934T762KNF1V%29&_kx=8G3OumshLvEfThcp28ReRczuzrPAIU-MWOpNcx5ueGO9Kp14cLaD_i0UpkDn7gGP.J8JtEm



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Exercise

Study finds weed users get more active than abstainers

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Step aside, harmful imagery of a couch potato stoner flattened into flapjack.

Cannabis use of all kinds correlates to increased light physical activity—like, say, hacky-sack, disc golf, yoga, or bedtime activities. Just follow the science.

A large, new study found cannabis use in adults correlates to increases in certain types of physical activity. And no amount of pot use increased sedentary behavior compared to a control group.

This research builds on previous studies debunking cannabis’ bad reputation for creating couch potatoes. 

researchers found that daily blazers had a 4% increased chance of light physical activity. 

Cannabis’ real impact on activity 

The recent study (Xue, 2024), published in the journal Cannabis and Cannabinoid Research, offers the largest sample size looking into this question to date. It included 4,666 adults aged 18 to 59. 

To learn more, researchers in this study analyzed data from FitBit-type devices—wrist-worn accelerometers—that track physical activity levels 24/7. They also included data on self-reported cannabis use from the last 30 days. 

By comparing these two factors, they determined whether self-reported cannabis use correlates with increases or decreases in sedentary behavior, light physical activity, or moderate to vigorous activity. 

The researchers also controlled for factors that could muddy the results, like co-use of other drugs like alcohol, race and poverty, and medical factors. 

Tap the image to peruse the readers’ choices

Cannabis tied to more activity—not less

The results (both before and after adjustments) found recent cannabis use did not cause couch potato-ism. 

Scientists did not find an association between weed use and increases in daily sedentary time. Instead, researchers found that daily blazers had a 4% increased chance of light physical activity. 

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The results also showed no differences in sleep time or moderate to vigorous daily activity between those who used cannabis and those who didn’t.

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Age did shift the associations. When broken down into two groups—18-39 year olds, and 40-59 year olds—some differences stood out. 

Both groups of tokers moved more than average. But after adjusting for age, only the youths got moving—the 18-39 year olds. Still, ganja did not make the older group slack off. The 40-59 year-old tokers showed no differences in sedentary behavior or physical activity from the control group of abstainers of the same age. 

These results suggest that cannabis use may increase light physical activity for young adults, but have no significant effect on activity by mid-life. Regardless, there is no evidence here that cannabis will leave you stuck to your couch. 

Frequent cannabis users moved more than lightweights

Does Oregon have good Jack? You bet. Jack Herer from Midnight Fruit Co, Oregon. (Ryan Herron/Leafly)
An energetic Jack Herer from Midnight Fruit Co, Oregon. (Ryan Herron/Leafly)

Researchers also looked at whether participants puffed lightly, moderately, or tough.

None of the smokers—light, medium, or heavy—sat around more than the non-smokers. And get this—the frequent smokers went on more hikes than the occasional smokers. 

To repeat: the cannabis-using groups were not more sedentary than controls. Occasional cannabis use was more associated with sedentary time than those who used cannabis frequently.

The authors suggest this may reflect different motivations for cannabis use (such as frequent medical use vs occasional recreational use). It also might have to do with daily smokers better tolerating and incorporating cannabis than the occasional party puffer.

What’s your motivation?

While encouraging, this study did have a few limitations. 

For one thing, it relied on self-reported cannabis use which may introduce biases. It also didn’t include factors like the motivation for use. This factor might shift things, given that people sometimes use cannabis to treat conditions that limit physical activity—or sometimes as an aid for exercise. 

Reviewers on Leafly describe smoking a bowl, wanting to stretch, and get some gardening done. And good for them.

Background: A decades-old, pernicious myth of Reefer Laziness 

The anti-drug movement posits that using too much weed will leave you lazy and sedentary.

Perhaps you even remember this classic DARE ad, where weed flattens one girl into a couch. Even the family dog started talking trash in later ads. 

Thankfully the Xue, 2024 study is starting to get at reality.

We know that being sedentary is tied to a lot of negative health outcomes, including cancer, diabetes, and obesity. And in the US, most adults need to move around more each day. So, if cannabis use does lead to being sedentary, using it would be an added health risk. 

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There has been some evidence (Vancampfort, 2019) pointing to increases in sedentary behavior (Doggett, 2019) for teens using cannabis from ages 12-18. 

It suggests that cannabis-using teens spend more time on the internet, texting, or playing games. While this is much different than melting into an unrecognizable blob on the couch (as the DARE propaganda suggests), it does cause some reason for concern. Still, this evidence doesn’t take into account factors like mental health which could explain both early cannabis use and sedentary lifestyles. 

The good news—legalization causes teen use to go down; for a variety of reasons including requiring valid ID for purchase.

Adult studies have had more mixed findings. For example, one study (Vidot, 2017) found adult cannabis use correlated to less physical activity. But a longer, more recent study (Smith, 2021) found that cannabis use correlates to MORE physical activity.

Now, the biggest study so far suggests that cannabis does not correlate to being a lazy loser. If anything, it may help you get a little more activity in your day.

See you at the Frolf course. Fore!

Ten fun light activities to do high

Low angle view of a womans step as she walks on a road lined with beautiful colorful autumn trees with sunlight coming through the leaves.
(Gajus/Adobe Stock)
  • Go for a walk or hike
  • Get some chores done
  • Get out into the garden
  • Play kickball with the kids
  • Play four-square
  • Neighborhood litter clean-up
  • Play some hacky-sack
  • Hit the disc golf course
  • Yoga and stretching
  • Complete our list—type in your favorite light activity when lit in the comments below.



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New study: People got high without any munchies on THC-V

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Top Takeaways

  • There’s a molecule in weed being dubbed diet weed—“THC-V”
  • Some evidence exists that THCV gets you high without the munchies
  • This study supports that finding, but in a weak way
  • More research is needed

Read below as Leafly science writer Nick Jikomes, PhD digs into the latest hype study.


THCV is a minor cannabinoid that’s acquiring a reputation as “diet weed.” You can find it described this way online based on historical studies linking it to appetite suppression. Excitement has spiked again with the conclusion of a yet-to-be-published, privately-funded, double-blind, human study. The results have been reported like this: “THCV increases energy and motivation without marijuana’s ‘munchies’ effect.”

What, exactly, did this study find? Are the results robust, and how do they fit into the wider picture of what we know about the biological effects of THCV? To understand, let’s review what’s been shown historically, using that to understand the latest findings. 

Pink boost goddess from Emerald spirit botanicals
Emerald Spirit Botanicals’ Pink Boost Goddess has record-high THC-V in California. (Courtesy Emerald Spirit Botanicals)

CB1 Receptors, cannabinoids & eating

It has long been known that THC stimulates appetite in the short-term. “The munchies’” are well-known to cannabis consumers and there’s considerable research demonstrating THC’s ability to stimulate appetite. This effect comes from the CB1 receptor of the endocannabinoid system. Stimulating CB1 reliably elicits feeding. This can be achieved by exogenous plant cannabinoids like THC, endogenous cannabinoids like anandamide, or synthetic CB1 activators used in scientific research. In other words, there is a general tendency for CB1 activators to induce feeding (“hyperphagia” is the technical term). 

Preventing CB1 receptor activation tends to have the opposite effect. If you engineer animals that lack CB1 receptors entirely, they are lean and resistant to diet-induced obesity. If you block the CB1 receptor with drugs, this tends to reduce appetite (“hypophagia”)—animals eat less.

The ability of THC and other CB1 activators to induce feeding is dose-dependent. In general, lower doses induce less feeding, higher doses more (up to a point). An interesting wrinkle in the equation between CB1 receptor stimulation and feeding is that drugs like THC don’t merely impact total feeding levels, but patterns of food intake over time. For example, recent work has shown that THC vapor induces an acute (short-term) increase in feeding in rodents, which is then followed by a compensatory reduction in food intake over longer time periods. The net effect is that there’s no overall weight gain, which may explain why human surveys tend to find a negative correlation between cannabis consumption and obesity.

human surveys tend to find a negative correlation between cannabis consumption and obesity

Bottom line: CB1 receptors are critical for appetite, and any drug that affects CB1 receptors is likely to affect appetite. As I’ve explained in more detail elsewhere, CB1 receptors are located throughout the body, influencing many aspects of metabolism.

How does THCV affect the CB1 receptor? 

  • If it activates CB1, we would expect THCV to induce a short-term increase in feeding. 
  • If it blocks CB1, we would expect a short-term decrease in feeding. 
  • The answer: it can do both. 

There is evidence that, at low doses, THCV behaves as a CB1 receptor antagonist, blocking the receptor. At higher doses, it can behave as an agonist, activating CB1. We would therefore expect relatively low doses of THCV to suppress appetite in the short-term, and higher doses to enhance it. 

What happens when you give relatively low doses of THCV to animals? Researchers have shown that pure THCV has been shown to induce hypophagia (eating less) and weight loss in rodents, similar to synthetic CB1 blockers. No surprise there–if THCV blocks CB1 receptors, that’s what we expect. An interesting twist in that study: when the same dose of THCV was applied in the form of a whole-plant extract, instead of pure THCV, the effect went away. In other words, the THCV extract did not produce a significant change in body weight or food consumption. Why? One possibility is the presence of small amounts of THC in whole-plant extracts. Because both THC and THCV interact with CB1 receptors, they “compete” with each other for access to the receptor. As a result, the relative ratio of THC and THCV becomes important for determining the net effect.

Related

Can THCV really curb the munchies?

What happens when you give THCV to humans? In one historical pilot study, researchers gave small doses of THCV to patients with type II diabetes (5 mg, twice daily for 13 weeks). Compared to placebo, THCV induced a statistically significant effect on fasting glucose levels and pancreatic β-cell function. That result is relevant to the treatment of diabetes and related effects on insulin sensitivity have been observed in mice. However, it did not have a significant impact on appetite or body weight. A major caveat of that study is that it was small–only 10-14 patients were in each experimental group, each on a different combination of prescription diabetes drugs. 

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In summary, THCV has been shown to block CB1 receptors at certain doses and animal research has observed an appetite-suppressing effect. However, the small human trial described above failed to show such an effect. It’s possible an effect would be seen with a different dose or in a metabolically healthy population. Both dose and the presence or absence of other drugs are important variables to consider, as we’ll see below.

The latest human research on THCV: Does it show a suppression of hunger?

Phylos Biosciences helped fund a double-blind, placebo-controlled crossover trial thatgave 78 adults different combinations of placebo, THC, and/or THCV for three days at a time. Patients ate the drugs in the form of gummies. “Crossover trial” means that each group of participants got each combination of drugs on different weeks. The drug combinations used:

  • Placebo (no cannabinoids)
  • THC only (5 mg)
  • THC (3.4 mg) + THCV (5 mg)

Notice some details: 

  • There is no THCV-only condition
  • The combination THC + THCV condition involves a lower dose of THC (3.4 mg) compared to the THC-only condition (5 mg)
  • The THCV dose used (5 mg, once per day) was less than what was used in the other study we looked at above, which saw no effect on appetite (5 mg, twice daily). 

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Let’s first describe the headline result. After that, we’ll critically evaluate the results and whether we can take them to the bank. From the study abstract:

“Both THC and THCV + THC increased subjective energy, activity, exercise performance, and well-being compared to placebo… with the THC-only intervention increasing hunger in full doses. THCV ameliorates the increase in hunger associated with THC consumption.”

What they’re reporting here is that 5 mg of THC increased hunger levels. No surprise there. This dose of THC has been shown to stimulate appetite before, which is what we’d expect based on a wealth of literature. When they say, “THCV ameliorates the increase in hunger associated with THC,” that means that in their combined THC + THCV condition, people got less munchies than normal.

The analyzed data are not available in the published abstract and methods. Below are some numbers from a recent press release (the full study has not been published yet, to my knowledge). Note that the THCV gummy they used comes from a strain marketed as, “Get Sh!t Done™” (GSD):

  • 20% more participants felt energized after consuming the GSD gummy compared to placebo.
  • 40% more participants reported enjoying their daily activities after consuming the GSD gummy compared to placebo.
  • Participants who consumed the THC-only gummy reported a 50% increase in hunger when taking full doses.
  • Participants who consumed the GSD gummy did not report a statistically significant increase in hunger compared to placebo.
  • Participants who consumed the THC-only gummy reported feeling fatigue three times more than the GSD group.
  • Participants who consumed the GSD gummy reported significantly less fatigue than placebo.
  • Both GSD and THC-only gummies increased activity, exercise performance, motivation, and well-being compared to placebo.
  • There was no THCV-only option
THCV vs THC molecular structure (Illustration/Leafly)

Notice how the team describes the results. More participants are said to have felt energized and enjoyed their daily activities With the GSD (THCV) gummy compared to placebo. Remember: there is no THCV-only condition. Finding that people who consumed the GSD (THCV) gummy reported more energy and enjoyment of activities does not mean that the effect came from THCV—it came from THCV together with THC. 

Similarly, when they say, “Participants who consumed the THC-only gummy reported feeling fatigue three times more than the GSD group,” what this really means is that more fatigue was reported in response to 5 mg of THC compared to 6.5 mg of THCV together with 3.4 mg THC. 

The hunger result must be similarly parsed: “Participants who consumed the THC-only gummy reported a 50% increase in hunger when taking full doses. Participants who consumed the GSD gummy did not report a statistically significant increase in hunger compared to placebo.” 

That translates to: those who consumed 5 mg of THC reported a 50% increase in hunger, while those who consumed only 3.4 mg THC together with 6.5 mg of THCV reported no hunger increase compared to placebo.

Because there is no THCV-only condition and two different doses of THC were used in the THC-only vs. THC + THCV condition, the results cannot be clearly interpreted. 

Bottom line: We need to isolate THC-V’s effects from THC

We know that THC’s psychoactive effects, including on appetite, are dose-dependent. Therefore, the differences they report in energy levels, hunger, and fatigue can all be explained by the difference in THC dose. You would expect a lower dose of THC (3.4 mg) to induce a different level of hunger and energy/fatigue than a higher dose (5 mg). It would be surprising if it didn’t.

These results would have been more readily interpretable if they had kept the THC dose at 5 mg in both groups, and added a THCV-only group as a further control. Assuming the results are replicable, we cannot know whether the differences they saw between groups had anything to do with the presence of THCV, or were entirely due to the two doses of THC used.

There are interesting hints in the literature that THCV may have important effects of metabolism, including appetite-suppressing effects in rodents. But before we conclude that “diet weed” has been discovered, more diligent research is in order.



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anxiety

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

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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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