Meds Physical Effects of Cannabis

[momofthegoons]

How Your DNA Affects Your Response to Cannabis - The CYP2C9 Gene​

Updated June 9th 2020

Quick Summary: A gene called CYP2C9 makes an enzyme that breaks down THC (the main psychoactive ingredient in cannabis). Variations in this gene can cause a 3-fold difference in your ability to metabolize THC. Studies have shown that this can cause differences in how long-lasting and intense the effects of pot are for different people.

Also, your CYP2C9 variant may help predict how long you have to wait to pass a drug test after consuming cannabis, with certain genetic variants only needing a few days to clear the relevant molecule from their system and others needing up to 30 days.

Mapping the Human Genome: A Personalized Wellness Revolution​

The landscape of medicine and wellness is quietly undergoing a radical transformation. Since we mapped the human genome in 2003, tens of thousands of studies, in different ways, are pointing to the same conclusion:

Each human being's metabolism is unique. Generic dietary advice or using the same medical interventions for everybody just doesn't match up with the countless differences observed between people's individual biochemistry and metabolism.

In this article, you'll learn how the principles of nutrigenetics and pharmacogenetics can help you understand your high, help you understand your body, and even help you pass a drug test.

CYP2C9: Destroyer of THC​

CYP2C9 is a gene that contains instructions for building an enzyme also called CYP2C9. It is made by the liver and the GI tract. It is part of the Cytochrome P-450 family of enzymes.

Besides having one the coolest names around, the Cytochrome P-450 family of enzymes are all phase I detoxification molecules. This means they are responsible for the "first pass" of breaking down, or metabolizing, different substances. Cytochrome P-450 enzymes break down everything from prescription drugs to inhaled smoke to hormones like estrogen that our body produces on its own.

The chemical structure of the CYP2C9 enzyme is the perfect match for the chemical structure of THC, the main psychoactive molecule in marijuana. Because of this, as THC circulates throughout the body, when it comes in contact with CYP2C9, CYP2C9 chemically transforms THC into other molecules. When a substance is changed like this, the resulting molecule is called a metabolite.

The graphic below shows the chemical transformation catalyzed by CYP2C9. As you can see, it is a two-step process to break it down to the non-psychoactive metabolite, THC-COOH. You don't need to worry about any of the chemical structure to understand this well, just know that CYP2C9 converts THC to THC-COOH.

Based on this image alone, you might imagine that more or less functional CYP2C9 in your body might also change the amount of THC in your body after smoking.

Genetic Polymorphisms: What makes you, you.​

So, as you might have guessed already, we don't all have the same "version" of the CYP2C9 gene. Just like you have variations in your genes that cause your eyes to be blue or brown, you have variations in the CYP2C9 gene that create your own unique metabolism. These variations are called Single Nucleotide Polymorphisms, or SNPs for short. If you'd like to read more in-depth about SNPs, check out this article I wrote. For the purposes of this article, just know the following:

• SNPs are the commonly occurring variations in your genes. They are not mutations.
• SNPs are identified with an "rs" number. For example, rs1057910 tells us exactly where that SNP is located in your DNA.
• A SNP means that one letter of your DNA sequence varies from person to person.
• Your allele type tells us which version of the SNP you have and is written with two letters, such as AA, AT, or TT.

In the above example, the "C" allele in example 1 is replaced with a "T" allele in example two. This is a SNP.

It's fairly well-known that the cytochrome P-450 class of enzymes contain many SNPs, or variations, that change the function of each enzyme. For example, certain SNPs in the CYP2D6 gene are known to cause poor reactions to SSRI antidepressant drugs. And, a SNP in the CYP1A2 gene has a major effect on how long it takes to break down caffeine. This same SNP is also related to a 4-fold risk of high blood pressure and heart attack from excess caffeine consumption. Pretty significant stuff, right?

So, scientists thought it would be a good idea to test whether or not any SNPs in the CYP2C9 gene change the way we break down THC.

What the Studies Show​

The first study on the pharmacogenetics (fancy word for how your genes impact your drug metabolism) of THC and CYP2C9 was done in 2005. (Link here)

This initial study was done with the enzymes in a petri dish, not in human subjects. However, they found that the CYP2C9*3 version of the enzyme (produced by C allele carriers) metabolized 30% less THC than the CYP2C9*1 version of the enzyme (produced by A allele carriers).

If this seems confusing, just know that in the initial petri dish study, one version of the enzyme was found to be 30% less effective at breaking down THC than the other. Since this was not done on human subjects, the question was raised: Will this translate to having an effect in the human body?

CYP2C9 In Human Subjects​

A clinical study was done in 2009 which answered that question with a fairly definitive "yes". 43 healthy volunteers were given 15 mg of oral THC and levels of THC and it's metabolites 11-OH-THC and THC-COOH were measured over time. Additionally, their subjective response was reported. While this was a small study, its results were strongly significant.

It turns out that for each C allele someone carries, the less efficient the CYP2C9 enzyme becomes at breaking down THC.

So, CC carriers had on average THREE times more active THC in their system than AA carriers. AC carriers had roughly 2 times the THC of AA carriers.

You can see this in the graph below in the first column on the left.

Here's another way of visualizing it looking at blood levels of THC over time:

Furthermore, because THC is converted into THC-COOH by the same enzyme, CC carriers had on average only 15% of the inactive metabolite in their system compared to AA carriers. You can see that pretty clearly in the farthest box on the right in that first chart above. Now, this gets really interesting because THC-COOH is the metabolite most urine drug tests are looking for to register whether or not someone has been smoking pot recently. More on that later.

CYP2C9 and Your High: The Subjective Effects​

CC carriers reported more drowsiness and a longer effect from ingesting THC as shown by the graph below. Participants in the study reported their subjective experience over the course of 3 days. And, interestingly enough, CC variants showed a significant increase in drowsiness 72 hours later.

Since this study was done using orally consumed cannabis, its important to note the differences between smoking and eating edibles. When eating THC, the breakdown process starts in the gut, so CYPC29 starts doing it's job before you even get high. So, it effects both how high you get, and how long it lasts. When smoked, CYP2C9 has less effect on how high you get right off the bat, but still has the same impact on how long the effects last.

There are so many potential further areas of inquiry. Different methods of smoking combined with CYP2C9 variants. CYP2C9 variants combined with other genes. The list goes on, and hopefully a more relaxed research climate around cannabis in the coming years will yield other interesting and useful studies.

CYP2C9 and Drug Tests​

Contrary to popular belief, THC does not stay in your system for very long. Drug tests are looking for the THC-COOH metabolite, because it generally hangs around the body for about 30 days... UNLESS you have the CC variant of CYP2C9. Because so little THC gets converted into THC-COOH, there's hardly enough of it to register on a urine test to begin with. It appears that after just a few days, CC carriers could pass a urine test as opposed to the 30 days it takes AA carriers.

Note how little THC-COOH is present in CC carriers. THC-COOH is stored in fat, so there is much less to store to begin with and detoxify overall.

You might be asking, "if this study was done in 2009, why haven't I heard of it?" Well, the cost to get your DNA sequenced by 23andMe in 2009 was over $1000, making it much less accessible than it is now. Having this information just wasn't relevant to most people.

Note that I used to recommend 23andMe but DO NOT anymore due to their privacy policy and sale of their user's data for research. Additionally, they've changed their data set and it no longer contains certain key variants for wellness. Instead, I use the Apeiron Genomics Test and have created a proprietary endocannabinoid test that looks at 50+ variants. Contact me if you'd like to order it or sign up for the upcoming training if you're a practitioner looking to provide this type of information for your clients.

How Can I learn What CYP2C9 Variant I have?​

If you have your 23andMe done, you can look up your CYP2C9 variant by going to the tools -> raw data section of your 23andMe login page. Then, copy and paste this into the search bar: rs1057910

Then, it will tell you your variant: AA, AC, or CC

Here's a quick summary of the different variants:

AA - Most efficient CYP2C9 enzyme. Breaks down THC most fully and rapidly. Likely to experience the least amount of drowsiness from pot. Gets less high from edibles, high from smoking or edibles shorter in duration.

AC - Intermediate between AA and CC

CC - Least efficient CYP2C9 enzyme. Does not break down THC as completely. Likely to experience the most amount of drowsiness from pot. Gets WAY more high from edibles, high from smoking or edibles longer in duration.

Personally, I'm an AC.

What Else Does CYP2C9 Do?​

THC is far from the only thing that CYP2C9 is responsible for. Blood thinning medications like warfarin and non-steroidal anti-inflammatory drugs like ibuprofen are some of the other substances it helps break down. In fact, poor metabolizer variants of CYP2C9 have been shown to heighten the risk of intestinal bleeding from using ibuprofen. (Link Here) It's a pretty handy thing to know beyond just cannabis consumption.

Is this the only factor that influences how I feel about getting high?​

To this, I answer a a very clear “NO”. This is just one of the many factors that influence your response to cannabis. While this study is significant, it is only the very beginning of understanding the complex dynamics at play. For example, there are other SNPs in the same gene that might further influence how efficient your CYP2C9 is. Note that in the graphs above, there is still some variation between carriers of the same variant. Hopefully this will be explored by further genetic studies.

The breakdown of THC is only one small piece of how your body responds to cannabis.

For example a SNP...

• In the FAAH gene effect levels of craving after stopping smoking and greater or less neurological reward response to cannabis.
• In the COMT gene affects how impaired your short-term memory is after smoking herb. One variant scored 40% better on average than the other on cognitive testing.
• In SLC66A seems to effect better or worse decision-making skills after consuming THC, and in combination with COMT is a predictor of better or worse executive function.
• In PENK gene is associated with likelihood for cannabis dependence.
• And SNPs in the ATK1, CNR1, and ABCB1 genes are associated with higher or lower likelihood for negative or psychosis-like symptoms after consuming cannabis. (Hey, I get it, the first time I hit a vaporizer I thought I was going to die)

​

(If anyone is interested in having their genes analyzed, there is a link in the article to the author. Just follow title link and scroll to the bottom of the article.)

 

[momofthegoons]

WHY ARE SIDE EFFECTS TO CANNABIS MILD? HOMEOSTASIS AND THE ECS​

Bias in cannabis science has a problem, the endocannabinoid system (ECS) induces homeostasis. This means the system that cannabis responds to will provide balance and harmony to many other systems in the body. But to do this, cannabinoids often have to pit multiple functions against each other. Otherwise, most side effects to cannabis are countered by a positive benefit which makes it easy to cherry-pick good or bad data.

A negative-feedback loop occurs when an effect blocks the function and this is required for a homeostatic system. In the case of appetite and energy, the CB1 receptor releases ghrelin which causes hunger. But food intake releases another hormone known as leptin which competes with the endocannabinoid system (ECS).

Cancer and requiring the full-spectrum​

ECS therapy is sometimes best achieved by the whole cannabis plant, though. This is because the ECS comprises a system of receptors and signaling molecules, each uniquely affected by a wide variety of substances in the plant. For example, synergistic effects from terpenes such as caryophyllene and cannabinoids like CBG help to maintain homeostasis. That said, the perfect spectrum of constituents to induce homeostasis through the ECS usually depends on the person, the desired outcome, and a lot of factors science has yet to figure out.

Cancer is an example where homeostasis is critical during recovery, and where the full spectrum of cannabis can be utilized. That is, different cultivars (strains) will provide different effects. For example, a high THC variety will help turn off a switch that (non-hormonal) cancers rely on, whereas a CBD:THC blend will instead aid with the growth of healthy tissue.

Self-moderated tolerance​

The cannabinoid receptors keep themselves in check, too. An abundance of THC can still cause excessive activity across the CB1 receptor even though it is only a partial agonist. To compensate for any overactivity, CB1 receptors are temporarily shut down and CB2 receptors morph into place for further maintenance.

Inflammation on-demand by the ECS​

As it turns out, CBD can help protect from CB1 receptor desensitization by acting on the signaling protein, beta-arrestin. Whereas alcohol destroys certain receptors and that damage can be long-lasting if not permanent.

Homeostasis is sometimes maintained on-demand, which is a complex facet of endocannabinoid therapy. More often than not, anti-inflammatory properties are characteristic of the plant. This is so well documented that it might be perplexing to explain how the ECS can provide inflammation when necessary. Yet, endocannabinoids degrade into inflammatory metabolites that the body uses in emergencies, like when you break a bone.

Blood pressure side effects and cannabis greenouts​

Blood pressure, however, is one mechanism that an overloaded endocannabinoid system cannot keep in a homeostatic state. This is why hypotension is considered one of the few side effects of cannabis, the root cause for green outs. But this concern, alongside interactions with other drugs, is more problematic for minor cannabinoids that have not yet been documented in phase I clinical trials. And yet, well-run trials face the burden of bias in the cannabis space according to a study by the Consortium for Medical Marijuana Clinical Outcomes Research.

So, it seems that cannabis and endocannabinoid therapy sustain physiological balance more efficiently than humans can document science.

Show your work​

• The CB1 is biphasic, with early ERK 1/2 inhibition via beta-arrestin, and late-stage activation via the adenylate cyclase path.
• Chronic exposure to THC causes CB1 receptor desensitization. But THC also interacts with b-arrestin, a signaling protein that can limit receptor desensitization. CBD and possibly limonene have the potential to lower the need for tolerance breaks via b-arrestin.
• CB2R and GPR55 cross-talk negatively.
• Neuro-morphology after chronic cannabis use includes new CB2 receptors on microglial cells.
• Memory and focus: CB1 agonists and linalool inhibit acetylcholine, whereas pinene acts as an acetylcholinesterase inhibitor.

Sources​

1. Nguyen, P. T., Schmid, C. L., Raehal, K. M., Selley, D. E., Bohn, L. M., & Sim-Selley, L. J. (2012). β-arrestin2 regulates cannabinoid CB1 receptor signaling and adaptation in a central nervous system region-dependent manner. Biological psychiatry, 71(8), 714–724. https://doi.org/10.1016/j.biopsych.2011.11.027

 

[bulllee]

The entourage effect: Does it really exist?​

Nick Jikomes, PhDJune 8, 2022
Have researchers actually found an entourage effect? (Sasha Beck / Leafly)
Mind & Matter is a monthly column by Nick Jikomes, PhD, Leafly’s Director of Science and Innovation

The entourage effect is the idea that two or more drugs can act synergistically when consumed together, stimulating effects that would not be observed if they were taken on their own.


Cannabis-derived products typically contain more than just THC. Consumers often report that cannabis products offer effects not readily explained by THC content alone. Research has suggested that pure THC is not as well-tolerated by medical cannabis patients as botanical extracts. This has given rise to the notion of entourage effects in cannabis: THC is the main driver of psychoactive effects, but these effects can be modulated by other molecules. As a result, different forms of cannabis might have distinct effects depending on the specific ‘entourage’ of chemical compounds they contain.

The idea has captivated scientists and consumers, but is it true? Is there any clear evidence of entourage effects among any cannabis-derived cannabinoids and terpenes? Or between THC and other types of drugs?

What about psychedelic entourage effects among the various species of psilocybin mushrooms, which are also known to vary in their chemical content?

Known entourage effects with cannabinoids​

Early evidence for possible entourage effects with cannabinoids came from studies in the 1990s.

Led by Dr. Raphael Mechoulam, they looked at the endogenous cannabinoid 2-AG, which interacts with the body’s two main endocannabinoid receptors, CB1 and CB2. Scientists found that 2-AG was often present with other endogenous compounds, some of which could enhance 2-AG’s physiological effects in mice. This showed that ‘entourage effects,’ where one or more molecules enhance (or diminish) the effects of another, may be one way the endocannabinoid system is regulated at the molecular level.

One example of an interactive effect between two cannabis-derived cannabinoids is THC and CBD. THC activates the CB1 receptor of the endocannabinoid system, accounting for its psychoactive effects. CBD also interacts with this receptor but in a different way, changing CB1 such that it changesTHC’s ability to activate it. This probably accounts for CBD’s ability to mitigate some of THC’s side effects, such as paranoia and short-term memory disruption.

CBD mitigates the direct effects of THC

CBD mitigates the connection between THC and the body’s CB1 receptor. (Sasha Beck / Leafly)
Studies have shown that the THC:CBD ratio also influences the level of psychoactivity experienced by cannabis consumers. For infrequent cannabis consumers, when CBD is present at much higher levels than THC, intoxication is reduced compared to THC alone. Conversely, consumption of THC (8 mg) together with half as much CBD (4 mg) enhances the intoxicating effect, but only for infrequent consumers. In people who frequently consume cannabis, the intoxicating effects of THC don’t change much when combined with CBD. This indicates that the psychoactive effects of cannabis can change based on the THC:CBD ratio in a way that depends on your level of consumption experience.

There may also be entourage effects involving the impact of cannabinoids on pain. Full-spectrum cannabis products can show better efficacy and tolerability for pain patients compared to pure THC. The details still need to be worked out, but cannabinoids like THC may have interactive effects with opioids. Animal research has shown that when opioids are combined with cannabinoids, pain relief can be achieved using a lower dose of the opioid. More human clinical research needs to be done here, but synergy between cannabinoids and opioids may be one reason why states with medical cannabis laws tend to see reductions in the use of certain prescription drugs.

Entourage effects between cannabinoids and terpenes?​

Are cannabinoids the only factors in entourage effects? Maybe not.

There is speculation that terpenes, the volatile compounds that give cannabis its aroma, can modulate the psychoactive effects of THC. One of the most influential scientists popularizing this view is Dr. Ethan Russo, with whom I’ve spoken about cannabinoid-terpene interactions:


Two of the more widespread beliefs about cannabinoid-terpene entourage effects are:

1. Limonene provides antidepressant effects, brightening the effects of a THC high.
2. Myrcene provides calming or sedative effects, accounting for the couch-lock phenomenon many THC consumers are familiar with.

While intriguing, these claims tend to rest on thin evidence. In humans, the evidence is almost entirely anecdotal. There is no clear clinical evidence in humans that limonene or myrcene modulate THC’s effects in these ways, although clinical trials are now underway to assess this.

While there is some preclinical evidence that terpenes like limonene and myrcene may have psychoactive effects in animals, these studies typically involve injection of terpenes directly into rodents, at doses that may not resemble those seen with human cannabis consumption, and without co-administration with THC.

Myrcene is one of the most common cannabis terpenes. It’s not uncommon to hear that it promotes sleepiness. There are some animal studies investigating myrcene’s effect on sleep, but they involve injecting rodents with myrcene together with drugs like pentobarbital, a barbiturate with strong sedative effects. The results have generally not been replicated and sometimes show contradictory results, even within the same study, depending on the details of each experiment. While there may be good reason to expect that some cannabinoid-terpene entourage effects will be discovered, research to date is too sparse to draw firm conclusions about human cannabis consumption.

​

Private research also being done​

There is more data out there about cannabinoid-terpene interactions. Unfortunately, it’s owned by private companies who are unlikely to share it publicly. For example, I recently talked to Dr. Andrew Chadeayne, who ran R&D for a Colorado-based company called ebbu, Inc. (Ebbu was purchased by Canopy Growth Corp. in 2018.) Researchers at ebbu apparently did an exhaustive set of experiments looking for interactive effects among the major cannabinoids and terpenes found in cannabis. For example, they measured whether any terpenes enhanced or diminished the effects of THC at the CB1 receptor. Apparently some terpenes were able to significantly enhance THC’s ability to activate the CB1, which would be expected heighten its psychoactivity.


Cannabis and other plants communicate with the external world using the language of chemistry, but we are only just beginning to decode the meaning of this language. It will take years of study to understand what this chemical language means for human medicine and human experience.

“I like the piano analogy,” Dr. Andrew Chadeayne once told me, “where it’s like you’re not just playing one note but playing different notes. You start making chords. It’s this multifactorial sum of the pharmacology that creates the experience.”

Terpene function and entourage effects in nature​

One hint that terpenes may participate in entourage effects is that plants, fungi, and other organisms produce specific terpenes to serve their ecological needs. There are many examples. Sometimes a single terpene performs one clear function. Some plants (including certain cannabis cultivars) produce β-farnesene when attacked by aphids. Acting as an aphid “alarm bell” pheromone, it causes the pests to stop feeding and disperse. (Cannabis growers take note: if you’re having an aphid problem, consider growing something with high β-farnesene levels). There are also examples of synergy. Some potatoes, for instance, produce two similar antifungal compounds, with the antifungal effect of one boosted by small quantities of the other.


It’s also notable that plants like Cannabis tend to produce cocktails of terpene molecules in specific ratios. The fact that different “strains” expression distinct terpene combinations likely reflects that each descends from a particular lineage of plants adapted to a specific environment. Some specialize in defending against aphids, others against powdery mildew. The plants are playing chemical chords, not individual notes. A key step toward defining any bona fide cannabis entourage effects is therefore the map out which terpene entourages are reliably found in commercial cannabis.

Entourages in high-THC cannabis​

Scientists at the University of Colorado-Boulder and Leafly recently partnered to map the cannabinoid and terpene content of commercial cannabis. The results of this study elucidate the most common combinations of cannabinoids and terpenes found in the products used by consumers. If there are any robust cannabis entourage effects, we should be able to observe them through careful administration of the cannabinoid-terpene combinations associated with real products, at doses resembling naturalistic human consumption.

THC-dominant cannabis, containing little or no CBD, makes up ~96% of the commercial market for cannabis flower today. People just don’t buy very much high-CBD flower.


Among commercial THC-dominant samples, are there distinct entourages–combinations of cannabinoids and terpenes–that reliably show up? The answer is yes. In our study we used unbiased clustering algorithms to parse samples into statistically distinct groups based on their chemical phenotype (chemotype). We found that there are at least three distinct chemotypes of THC-dominant cannabisreliably present across US states.

What are they? Below are simplified summaries of each chemotype of high-THC cannabis, together with some additional information relating each one to popular industry labels, including Indica/Sativa and strain names. Listen to this talk for a deeper dive.

• Chemotype I–High β-Caryophyllene + Limonene. These samples account for ~53% of commercial THC-dominant Cannabis and have relatively high levels of the terpenes β-caryophyllene and limonene together with a mix of other terpenes. This chemotype was not preferentially associated with samples labeled “Indica” vs. “Sativa.” Strain names such as “Glue,” “Cookies,” and “Cakes” were among those over-represented for this chemotype.

Above: The The average terpene profile of Chemotype I.

• Chemotype II–Very High Myrcene + High Pinene. These samples account for ~34% of commercial THC-dominant Cannabis, having relatively high levels of myrcene and pinene. A popular example of a strain name over-represented in this chemotype is Blue Dream. Again, there was no clear bias for these samples to be “Indica” vs. “Sativa.”

Above: The average terpene profile of Chemotype II.

• Chemotype III–Very High Terpinolene + High Myrcene + Ocimene. These samples account for just ~13% of commercial THC-dominant Cannabis, with high levels of terpinolene. This profile is associated with mild levels of the cannabinoid CBG, at ~1% on average. Intriguingly, samples labeled “Sativa” were over-represented in this group, which came from a small subset of “Sativa” strain names, e.g. Lemon Haze, Jack Herer, and Dutch Treat.

Above: The average terpene profile of Chemotype III.
While some of the chemically-defined groups can be further split into sub-groups, these were the three chemotypes of high-THC cannabis most reliably present. In other words, they represent different entourages of cannabinoids and terpenes–ones that consumers are encountering with high frequency among commercial cannabis products. Do these entourages offer distinguishable psychoactive or medicinal effects? We don’t know. Someone needs to measure this in carefully designed, properly blinded, dose-controlled studies.

Potential entourage effects in psilocybin mushrooms​

Cannabis is not the only biological entity with the potential for interesting entourage effects. Psilocybe mushrooms are also of interest. Like cannabis, one drug accounts for most of its psychoactive effects: psilocin, the active metabolite of psilocybin. Also like cannabis, different species and strains contain different ratios of psilocybin and other compounds.

In addition to psilocybin and psilocin, Dr. Andrew Chadeayne told me about lesser-known alkaloids sometimes present: Norbaeocystin, baeocystin, 4-OH-tryptamine, norpsilocin, aeruginascin, 4-OH-trimethyl-tryptammonium. We know very little about these, although he did share an interesting anecdote about the mycologist Paul Stamets, who has consumed pure baeocystin:


Some Psilocybe mushrooms also contain compounds called β-carbolines, which are monoamine oxidase inhibitors (MAOIs). Pharmaceutical MAOIs were once a common prescription for depression but are rarely used today. Plant-derived MAOIs, which typically lack the dangerous side-effects of pharmaceutical MAOIs, are found in many plants. In fact, β-carbolines are one of the two key ingredients in ayahuasca. The other is the potent psychedelic alkaloid DMT, which is only orally active when taken together with MAOIs.


The presence of β-carboline MAOIs in some Psilocybe mushrooms is interesting because they might influence the metabolism of psilocin. The presence of MAOIs is expected to intensify or extend the duration of a psilocin trip, although this still needs to be formally demonstrated.

Are there other potential psychedelic entourage effects, involving different combinations of fungal alkaloids and MAOIs, which we might discover among the various species of magic mushrooms? It’s entirely possible. Psychedelic startups like CaaMTech are chasing these questions.

The current task for researchers interested in entourage effects, for both cannabis and magic mushrooms, is to map the entourages reliably present in nature and commercial products. From there, we must carefully measure whether distinct combinations offer unique psychoactive or medicinal effects.

There is still much work to be done before we crack the chemical codes of these organisms.

To learn more about Mind & Matter and listen to the podcast episodes that inspired this article, visit this link.

 

[momofthegoons]

DOES CANNABIS LOWER YOUR IQ?​

Does cannabis lower your IQ? According to a recent study published in the American Journal of Psychiatry, the answer is yes. According to the research, if you consume from childhood to midlife, your IQ lowers by 5.5 points. You also have memory and attention problems.

But how accurate are these findings?

Conflicting Studies​

Many studies have focused on cannabis and IQ. A 2001 study found no relationship between cannabis smokers and cognitive impairment. A 2005 study concluded the same thing.

Then some studies suggest the opposite. These studies often point to a smaller hippocampus in long-term users as proof that cannabis lowers your IQ.

The new study, which followed nearly 1,000 individuals in New Zealand from age 3 to 45, concludes that future research is needed to establish causation.

Does A Smaller Hippocampus Lower Your IQ?​

The hippocampus is the region of the brain responsible for learning and memory. We have two hippocampi, one for the left side of the brain and one for the right. The hippocampus plays a significant role in consolidating short-term memory into long-term memory. It is also crucial for spatial navigation.
In a famous study, neuroscientists discovered that London cab drivers had an exceptionally large hippocampus due to their ability to navigate 25,000 complex city streets from memory.
Researchers wanted to figure out the chicken and the egg problem. Does having to navigate London’s busy streets cause the hippocampus to grow? Or do people with a larger hippocampus become successful cab drivers?

Grey Matter Connection​

Assuming the most recent study is accurate, and that long-term cannabis use does decrease your hippocampus – does it matter?
Scientists associate a smaller hippocampus with a higher risk for dementia and Alzheimer’s. But it is also possible to grow your hippocampus through exercise and eating foods high in omega-3 fatty acids.
But research suggests the size of your hippocampus isn’t as crucial as the hippocampus’ connectivity and ability to communicate with other brain regions. And this improves through spatial training, such as memorizing and driving around London’s busy city streets.
A growing number of neuroscientists are starting to recognize what the research is saying. Changes in grey matter brain volumes and white matter work together to optimize cognitive function. Gray matter stashes neurons in specific brain regions, while white matter facilitates communication between different areas.

So Does Cannabis Lower Your IQ?​

So does cannabis lower your IQ or not? If the most recent study is accurate, it appears that if you begin in childhood and smoke well into your midlife, your hippocampus will be smaller than those who didn’t consume for all those years.
Of course, this is the result of the one study, and even it concluded more research was needed to establish causation.
But assuming the results are confirmed, what’s the difference between cannabis and other activities or lifestyle choices that will result in cognitive decline later in life?
And what if one combines cannabis with exercise, meditation or yoga? Do the activities that increase the size of the hippocampus offset the potential damage cannabis does? Will a cannabis smoker who is physically active and eats healthy have a better outcome than a non-consumer who eats junk and never exercises?
And say a long-term cannabis user does have a smaller hippocampus. What does that tell us about their brain’s functional connectivity?
Easier for the corporate press to run the headline, “Cannabis Lowers your IQ,” than to question the epistemology of the research.

Footnote(s)​

Long-Term Cannabis Use and Cognitive Reserves and Hippocampal Volume in Midlife

Objective: Cannabis use is increasing among midlife and older adults. This study tested the hypotheses that long-term cannabis use is associated with cognitive deficits and smaller hippocampal volume in midlife, which is important because midlife cognitive deficits and smaller hippocampal volume...

ajp.psychiatryonline.org

https://www.sciencedirect.com/science/article/abs/pii/S1053811915009167

Acquiring “the Knowledge” of London's Layout Drives Structural Brain Changes

The last decade has seen a burgeoning of reports associating brain structure with specific skills and traits (e.g., [1–8]). Although these cross-sectional studies are informative, cause and effect are impossible to establish without longitudinal investigation of the same individuals before and...

www.cell.com

Neuropsychological performance in long-term cannabis users - PubMed

Some cognitive deficits appear detectable at least 7 days after heavy cannabis use but appear reversible and related to recent cannabis exposure rather than irreversible and related to cumulative lifetime use.

pubmed.ncbi.nlm.nih.gov

Neurocognitive consequences of marihuana--a comparison with pre-drug performance - PubMed

In determining the effects of regular marihuana use on neurocognition, abilities within specific relevant cognitive domains prior to regular drug use have not been available. The present study examined effects of current and past regular use of marihuana in subjects for whom pre-drug performance...

pubmed.ncbi.nlm.nih.gov

 

[momofthegoons]

The only time I've felt any sort of 'hangover' from weed is when I do edibles. And it's not the traditional 'hangover' feeling, it's more that I wake up still a bit high. It quickly passes with some coffee though. It's certainly never as debilitating as an alcohol hangover.

Marijuana Isn’t Associated With ‘Hangover’ Effects, Raising Questions About Driving And Employment Policies, Study Finds​

A new scientific review is challenging the idea that there’s a marijuana “hangover” effect the day after use, raising questions about policies that punish drivers and people in safety-sensitive positions for cannabis consumption that occurs weeks prior to drug tests being administered.

Researchers at the University of Sydney reviewed 20 studies that looked at the effects of marijuana eight hours after use, focusing on performance assessments. Their findings are set to be published in the journal Cannabis and Cannabinoid Research.

“Most studies didn’t detect ‘next day’ effects of cannabis use, and the few that did had significant limitations,” study author Danielle McCartney said in a press release. “Overall, it appears that there is limited scientific evidence to support the assertion that cannabis use impairs ‘next day’ performance. Though, further research is still required to fully address this issue.”

A total of 350 performance assessments were administered throughout the 20 studies that were reviewed. Only 12 of those tests (or 3.5 percent) found a significant hangover effect—and none of those involved randomized, double-blind, placebo-controlled methods. They were also all more than 18 years old.

“A small number of lower-quality studies have observed negative (i.e., impairing) ‘next day’ effects of THC on cognitive function and safety-sensitive tasks. However, higher-quality studies, and a large majority of performance tests, have not.”

“We can’t really comment on the magnitude of these effects because they weren’t all that well reported,” McCartney said. “They didn’t appear to be associated with a specific dose of THC, route of THC administration or type of assessment.”

The researchers said that their findings are notable in the context of evolving policies on driving and employment for cannabis consumers.



There have been some who’ve argued that a person shouldn’t drive or work in a safety-sensitive position for at least a day after using marijuana, but the study “found little evidence to support this recommendation.”

“Policy makers should bear in mind that the implementation of very conservative workplace regulations can have serious consequences, such as termination of employment with a positive drug test,” the study states. “They can also impact the quality of life of individuals who are required to abstain from medicinal cannabis used to treat conditions such as insomnia or chronic pain for fear of a positive workplace or roadside drug test.”

A related issue that the researchers noted is that drug tests are only able to detect inactive THC metabolites that don’t reflect intoxication and can stay in a person’s system for weeks or months after use.

This issue has become a focus of policymaking as the legalization movement continues to spread. Certain sectors like the trucking industry have identified THC screening as a major contributing factor for labor shortages, for example.

The head of the American Trucking Association (ATA) recently discussed the problem with a congressional committee, arguing that lawmakers need to “step up” to address the federal and state cannabis policy conflict as the industry faces these shortages.

Tens of thousands of commercial truckers are testing positive for marijuana as part of the federally mandated screenings, recent data from the Department of Transportation (DOT) shows.

Meanwhile, a senator sent a letter to DOT last year seeking an update on that status of a federal report into research barriers that are inhibiting the development of a standardized test for marijuana impairment on the roads. The department is required to complete the report by November 2023 under a large-scale infrastructure bill that President Joe Biden signed.

Experts and advocates have emphasized that evidence isn’t clear on the relationship between THC concentrations in blood and impairment.

A study published in 2019, for example, concluded that those who drive at the legal THC limit—which is typically between two to five nanograms of THC per milliliter of blood—were not statistically more likely to be involved in an accident compared to people who haven’t used marijuana.

Separately, the Congressional Research Service in 2019 determined that while “marijuana consumption can affect a person’s response times and motor performance…studies of the impact of marijuana consumption on a driver’s risk of being involved in a crash have produced conflicting results, with some studies finding little or no increased risk of a crash from marijuana usage.”

Another study from last year found that smoking CBD-rich marijuana had “no significant impact” on driving ability, despite the fact that all study participants exceeded the per se limit for THC in their blood.