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What are the most active ingredients in hemp and cannabis?

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Delta-9 THC is the most common active ingredient in cannabis. And CBD is the second most common on the market today. But are THC and CBD the first and second most active ingredients in cannabis?

Two cannabis ingredients more active than D9-THC

CBN (cannabinol) and delta-8 THC, byproducts of THC-acid or CBD, lightly agonize CB1 receptors with less activity than delta-9 THC.

Pharmacologists use a binding efficacy measure to deduce a molecule’s activity on a receptor. At CB1 receptors, D9-THC is nearly two times more active than a minor variant of itself known as THCv. Albeit an agonist in small doses, THCv (tetrahydrocannabivarin) is more commonly known as a neutral CB1 receptor antagonist. Neutral antagonism and inverse agonism is still activity, though.

Different types of activity at receptor sites. Courtesy of Coll, A. 2013. (1)

Infamously, a minor ingredient in cannabis chemovars known as THCp is thirty-three times more active than D9. (2) However, hexyl-THC is also present in cannabis with an unknown affinity and efficacy. (3)

THCp is the most potent ingredient in cannabis, with hexyl-THC in second place. Yet, more research needs to confirm hexyl-THC’s affinity at CB1 receptors. Furthermore, THC-oct, also known as THCj, has not yet been seen in cannabis but is more active than THCp given its longer side chain.

The most active ingredient in hemp

CBD partially binds to and agonizes the therapeutic human cannabinoid receptor, CB2. But let’s not forget about one terpene and ingredient in most hemp and cannabis chemovars, b-caryophyllene — a full CB2 receptor agonist. B-caryophyllene does not directly affect CB1 receptors, whereas CBD works as a Negative Allosteric Modulator (NAM) at CB1 receptors. That means CBD changes how THC’s stone feels, reducing part of the CB1 receptor’s spectrum.

Hexyl-CBD is, however, also present in cannabis. (3) With a longer-side chain, hexyl-CBD is more active than its common cousin, according to studies in mice. And a renowned study documented the discovery of CBDp and THCp in chemovars from the Italian government a year earlier — but only tested the latter. (2)

Cannabimimetic activity

At the end of the day, efficacy and affinity at CB1 or CB2 receptors still cannot deduce the ‘activity’ of a cannabinoid. Cannabidiol is broad, affecting a large umbrella of biological mechanisms. The promiscuous cannabinoid, therefore, is often descriptive of CBD.

Then again, it is one of the most thoroughly studied cannabinoids. And more research on CBG (cannabigerol) has come to light in recent years, with CBC (cannabichromene) and other ingredients still in the background.

CBD protects the endocannabinoid known as anandamide, which partially activates the CB1 receptor agonist. Likewise, ibuprofen and chocolate protect anandamide. In contrast, CBG protects 2-AG, an endocannabinoid that functions as a full CB1 and CB2 receptor agonist. Not surprisingly, drugs that protect 2-AG face delays due to their more broad cannabimimetic effect.

Furthermore, CBG and CBGa are both more potent COX-2 inhibitors than CBD, but not necessarily CBDa. The plant produces acidic phytocannabinoids, whereas COX-2 enzymes degrade the endocannabinoids.

What is the second most active ingredient in cannabis?

That question depends on many factors, and researchers can only make estimations at this time.

  • Efficacy at CB Receptors — Hexyl-THC (given THC-oct/THCj does not occur naturally.)
  • Activity at CB1 Receptors respective to abundance in current chemovars — CBN (cannabinol)
  • Activity at CB2 Receptors respective to abundance in current chemovars — Beta-caryophyllene
  • General cannabimimetic — THCa (with full spectrum extract) (4)
  • Most sites affected — CBD

Opining that CBD is the second most active ingredient in cannabis exposes two problems in cannabis science and endocannabinology. Firstly, the quantified answer to photodynamic activity is not straightforward. Secondly, the answer is not known.

Let us know in the comments what you think defines a cannabinoid’s activity level. And check out this story to learn more about hexyl-THC.

Sources

  1. Coll, Anthony. (2013). “Are melanocortin receptors constitutively active in vivo?”. European journal of pharmacology. 719. 10.1016/j.ejphar.2013.04.051.
  2. Citti C, Linciano P, Russo F, et al. A novel phytocannabinoid isolated from Cannabis sativa L. with an in vivo cannabimimetic activity higher than Δ9-tetrahydrocannabinol: Δ9-Tetrahydrocannabiphorol. Sci Rep. 2019;9(1):20335. Published 2019 Dec 30. doi:10.1038/s41598-019-56785-1
  3. Linciano P, Citti C, Russo F, et al. Identification of a new cannabidiol n-hexyl homolog in a medicinal cannabis variety with an antinociceptive activity in mice: cannabidihexol. Sci Rep. 2020;10(1):22019. Published 2020 Dec 16. doi:10.1038/s41598-020-79042-2
  4. De Petrocellis L, Ligresti A, Moriello AS, et al. Effects of cannabinoids and cannabinoid-enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes. Br J Pharmacol. 2011;163(7):1479-1494. doi:10.1111/j.1476-5381.2010.01166.x





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All about Cannabis

Reviewing the Cannabis Act – Cannabis | Weed | Marijuana

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Justin Trudeau’s hashtag government is finally reviewing the Cannabis Act – a year late.

They want to know: has cannabis legalization been successful?

Not in the sense of whether it’s been working for those who buy, sell, and consume cannabis. No, according to the Liberal’s Cannabis Act, the review must focus on Indigenous people, home growing, and whether legalization has helped the children.

After all, it was never about your right to your body. Post-COVID, it’s clear that freedom doesn’t exist. It’s a privilege handed out whenever the corporate state sees fit.

According to Justin’s Health Minister, this review will be “inclusive” and “evidence-driven.” And the result will “strengthen the act so that it meets the needs of all Canadians while continuing to displace the illicit market.” 

You can see the problem here.

Reviewing the Cannabis Act – a year late.

Reviewing the Cannabis Act

Reviewing the Cannabis Act is a year late. The Liberals said they’d do it three years after legalization. Nevertheless, it’s here. 

A couple of federal ministers announced how the Liberals would be reviewing the Cannabis Act. Like the Legalization Task Farce, there will be an “expert panel” led by retired career bureaucrat Morris Rosenberg.

Rosenberg is well-liked across the board. Everyone expects him to do a competent job.

And he might. But any recommendations can be ignored by Justin Trudeau’s hashtag government. Reviewing the Cannabis Act may not yield any positive results for anyone.

The government hasn’t named the other members of the “expert panel.”

Confines of the Review 

Reviewing the Cannabis Act

The issue with reviewing the Cannabis Act is that the Act itself demands “dual objectives of protecting public health and maintaining public safety.”

“Public health” means more of the same political spin about cannabis’ alleged harms and impact on children and indigenous people. Interesting that the federal government needs to hold the hand of these two identity groups.

I thought children had parents and mentors who looked after them. And aren’t indigenous people free, adult human beings?

This is why Justin Trudeau’s government is a hashtag government. They care more for optics and sound bytes than substance—they fake sincerity.

And this causes real-world destruction.

Look at the amount of plastic waste the Cannabis Act has created. Combined with face masks showing up in the ocean, fertilizer mandates, and not building pipelines, Justin Trudeau’s hashtag government has been a net negative for the environment.

Justin, his cronies and supporters don’t understand that fossil fuels are necessary to transition off fossil fuels. You can’t dictate consumer demand and expect the market to follow.

This hubris is why the illegal cannabis market still exists.

The “public health” approach to cannabis prevents BC Bud from operating aboveboard.

Cutting bureaucratic red tape and refocusing legalization away from “public health” and toward a viable commercial industry needs to be done.

What Canadians choose to do with their bodies is of no concern to the federal government.

Reviewing the Cannabis Act: 18 Months Later

Reviewing the Cannabis Act is not only a year late, but they expect the “expert panel” to take 18 months to conclude.

The problem is, with the current excise tax regime, many smaller producers won’t last. 

The government hasn’t rewarded those who have tried to play by the rules.

And that’s the problem in a nutshell. If you want to displace the “black market,” you must make it worthwhile for those individuals to get licences.

But when even the large licensed producers complain about an overtly restricted regime, what incentive does BC Bud have?

Reviewing the Cannabis Act means an “expert” panel will spend 18 months and hundreds of thousands of taxpayer dollars focusing in the wrong direction.

Fortunately, alongside public health busybodies, the panel will also hear from the cannabis industry and the general public.

So there’s an opportunity to turn the tide. Direct the narrative away from concern about children, edibles, and home-growing to excise taxes and a bloated bureaucracy.

Ottawa doesn’t license craft brewers in British Columbia. It has no business doing the same for cannabis.

Footnote(s)





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Making Sense of the COVID Cannabis Surge  – Cannabis | Weed | Marijuana

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How can we make sense of the COVID Cannabis surge? As reported previously, a pandemic-induced cannabis bubble has now burst. Total market cannabis sales are now in decline but what’s happened is a return to pre-pandemic market conditions.

We can answer some pressing questions using real-time sales reporting from Headset Insight. Namely, did we see a more significant decline in transaction volume or transaction size?

Which products fared best and worst during the last couple of years? And which customers are now buying less cannabis than they were in 2020 and 2021.

Digging into these underlying issues reveals patterns we can discern from the data. We know the COVID cannabis surge was real, so let’s discuss the details.

Decreases in Cannabis Transactions 

COVID Cannabis Surge

This graph shows the monthly transaction volume of the median store in four markets (California, Colorado, Oregon and Washington). Previously, Headset marked mid-summer as the turning point for when sales begin to stagnate and decline.

You can see that point marked by a grey dotted line.

Transaction volumes have been steadily declining. For example, the California median store transaction volume dropped from 7,309 transactions in July 2021 to 6,106 transactions in July 2022.

COVID Cannabis Surge – Shrinking Baskets

COVID Cannabis Surge

Again we look at the median store in each of these US cannabis markets. This time we’re looking at the average transaction or basket size trend. (Basket size is a measurement describing how many items a consumer purchases in a single transaction).

Similar to the previous graph, there is a steady decline across all markets. Consumers are spending less overall on each trip to the cannabis store.

The average basket size at a median Colorado store in July 2021 was $59.73.

In July 2022, it was $55.21.

This means that the COVID cannabis surge was indeed a pandemic-related consumer response.

Transaction volume vs. Transaction size 

COVID Cannabis Surge

Decreasing transaction volume and shrinking baskets have both contributed to overall sales declines. But which one is causing the most impact?

The chart above compares relative declines in median store transaction volume and average basket size by state from July 2021 to July 2022.

In every market, the relative decrease in transaction volume is more significant than the relative decrease in basket size.

This decrease implies that the reduced number of transactions has had a more significant effect on sales than shrinking baskets.

Of course, this depends on the market. In Colorado, for example, the retraction in overall transaction volume is nearly double the decline in basket size. Whereas, in Washington, these two data points are almost identical.

Category performance in California 

It can be tricky discovering sales trends among the different product categories. Diving into the data, we can see what’s contributed to recent downturns in top-line sales.

The chart above shows the year-over-year sales growth of different products in California. It then compares it to total market growth over the same period.

Flower, of course, performed well. From July 2019 to July 2020, flower sales growth rates were nearly double of the overall California market. This is the COVID cannabis surge in action.

Drinks and vape pens have maintained positive growth while topical and tinctures sales are decreasing.

Category Performance in Washington 

Washington’s cannabis market performed similarly to California’s. Flower saw a massive increase in early 2020, a poster child for the COVID cannabis surge.

Flower is now correcting while drinks and vapes remain consistent. Like California, tinctures are on the decline. But, unlike California, the topical category saw positive growth. 

Trends among top cannabis spenders before and after the COVID Cannabis surge

Who helped create the COVID cannabis surge? Top cannabis consumers spend more than average and contribute a disproportionate percentage of revenue to the cannabis industry.

This graph shows the median total spending of the top 10% of cannabis consumers over three months (May to July) over the past four years.

These customers have the greatest (relative) influence on top-line sales. For example, the top 10% in California have accounted for 30% of all cannabis sales this year.

On average, the top 10% also spent $100 more during the COVID cannabis surge than in 2019.

This trend shows that the top-tier cannabis buyers were influencing the COVID cannabis surge by purchasing more cannabis than average. This trend now appears to be in decline.

Cannabis customers compared 

The graph above compares the top 10% with the rest of the group. Here, we can reach the 10% with the bottom 90% and how it relates to the COVID cannabis surge.

In 2020, all cannabis consumers increased their spending. This is what we mean by the COVID cannabis surge. 90% of customers in California increased their spending just as much as the top 10% did.

In 2021, all groups had flat year-over-year growth in spending.

As the COVID cannabis surge officially ended by 2022, the differences between these two customer types are apparent.

In both Washington and California, the summer spending of the median customer in the top 10% decreased significantly more than that of the median customer in the bottom 90%.

Cannabis’ biggest spenders are tightening their belts. This is causing top-line market retractions.

COVID Cannabis surge broken down by age

All age groups follow a similar pattern. Generation X had the highest spending levels, while Millennials still contributed the most considerable total revenue.

Year over year growth in median customer spending during the May-June period is graphed above. During the 2020 COVID cannabis surge, younger customers spent more. This may be because older generations were less willing to venture outside the house and visit a retail shop.

Median customer spending held flat in 2021 across all age groups.

So far in 2022, most age groups have averaged similar decreases in spending. One exception is Generation Z which has the most significant reduction in total spending at -11%.

This data suggests that the youngest customers were also fuelling the COVID cannabis surge in early 2020.

In Summary

The COVID Cannabis surge is over. We see this with decreases in both transaction volume and basket size. However, reductions in transaction volume have a greater influence.

Flower remains the most volatile, with massive surges early in the pandemic with significant corrections in 2022.

Beverages and vape products have remained the most consistent during the rise and fall of the COVID cannabis surge.

The top 10% of cannabis consumers increased their spending in 2022 but decreased their spending in 2022 more than the bottom 90% of customers.

Younger customers were also responsible for the COVID cannabis surge. But customers across all age groups are now reducing their spending at more or less equal rates.

Footnote(s)

https://www.headset.io/industry-reports/understanding-the-recent-sales-declines-in-legacy-cannabis-markets





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Cannabis in the US Midterms (2022) – Cannabis | Weed | Marijuana

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What role will cannabis play in the USA 2022 midterm elections?

America’s burgeoning yet constricted cannabis industry hopes to see some change in Washington before the midterms reshape the political landscape.

America’s cannabis industry hopes to see the SAFE Banking Act passed. This legislation would provide cannabis companies access to financial services.

“Really what it comes down to is how important is cannabis for the Democrats to pass,” says Nawan Butt, Portfolio Manager at Purpose Investments.

Cannabis in the US Midterms: Incremental Reform

Cannabis in the US Midterms (2022)

Earlier this year, Senate Majority Leader Chuck Schumer introduced the Cannabis Administration and Opportunity Act (CAOA). The CAOA is comprehensive legislation aimed to legalize cannabis recreationally across the United States.

Schumer’s positioning on cannabis law reform has influenced stocks, but the Democrats haven’t delivered so far. Observers and experts have criticized the CAOA for numerous reasons. Most notably, a 15% excise tax would be levied in addition to state-level taxes.

For this reason, cannabis reformers have seen more success in incremental steps.

“Incremental reform has been defined as a mix of the SAFE Banking Act, plus social equity provisions, added on top of that to appease more left-wing Democrats,” says Nawan.

“We think there is work being done on a SAFE Banking Plus Bill, which is going to include the basics of the SAFE Banking Act. Which helps a lot of corporations get access to financial services and allows greater investor access to cannabis-related businesses.

“We think it’ll also have some social equity provisions in it. Which lays the foundation for spending a lot of the taxation that’s collected toward rehabilitation, as well as social equity and social justice programs for those adversely affected by cannabis laws in the United States.”

Promising Republican Poll

Cannabis in the US Midterms (2022)

If the midterm results are Republican majorities in the House and Senate, then the GOP may push cannabis reform aside until the 2024 general election.

“We don’t think this [cannabis reform] would be an item that the Republicans will prioritize,” says Nawan. “It’s not that they don’t support it. If we take a look at GOP support, they do look at cannabis as a positive.”

Recent polling of Republican voters found overwhelming support for cannabis legalization.

73% said there is no difference between the rights of legal cannabis businesses and that of any “regular” business. 76% of Republican voters agreed that the federal government should not interfere with individual states’ decision to legalize or decriminalize cannabis.

“So we can’t say GOP doesn’t support cannabis,” says Nawan. “There is a certain divide between the populace and the leadership, or the legislators. But overall, it’s either the Democrats pass it now or we’re going to see this being put off. At least until we have further insight into what the 2024 elections are going to look like.”

Cannabis in the US: Post-Midterms

Passing something cannabis-related after the midterms isn’t impossible. But it’s unlikely.

With a potential flip of the House and Senate to GOP control for the balance of the Biden presidency, “we don’t think this would be an item that the Republicans will prioritize,” says Nawan.

“If something doesn’t happen in the lame duck session, then we’re going to be pushing this out another 16, 18, maybe 24 months.”





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