TL;DR: Academic cannabis researcher who transitioned to work in the California cannabis industry. Here to announce our brand new nationally-distributed CBD brand Care By Design Hemp and answer all of your questions about cannabis, cannabinoids or working in the cannabis industry!


Hi Reddit! I am Dr. Matt Elmes, Cannabis scientist and cannabis enthusiast. I did my PhD in the Department of Biochemistry and Molecular Biology at Stony Brook University, where I studied how our bodies metabolize plant cannabinoids (such as THC & CBD) and endocannabinoids (the compounds our bodies naturally produce which THC ‘mimics’ to exert its psychotropic effects). The work done by me and my group identified ways that cannabinoids are transported to their respective metabolic enzymes inside of our cells. We first showed how this intracellular THC transport step happens in the brain, then later in grad school I went on to extend these findings to how it works in the liver. Our livers serve as the main site of phytocannabinoid inactivation so it is an important tissue for how we experience the effects of THC.

After grad school I accepted an industry-funded postdoc position with Artelo Biosciences doing preclinical drug development on a novel class of drugs that are able to alter our endocannabinoid system (ECS) signaling. By using a drug compound to block the molecular transport step that leads to our endocannabinoids getting broken down, we are able to temporarily raise the levels of endocannabinoid signaling in the brain and nervous system, which results in potent anti-pain and anti-inflammatory effects. The overarching goal was to create a new class of non-addictive, pain-killing drugs to help combat the opioid epidemic…and the ECS-boosting drugs my team and I created show remarkable efficacy in rodents! We’re only in the preclinical stages of drug development (and thus still quite far away from being considered as an FDA-approved drug), but I believe that ECS modulation strategies will prove to be a promising therapeutic avenue for many conditions that are suffered today.

During my postdoctoral work, some guy I had never heard of named Dennis Hunter reached out to offer me an interview for a position at his cannabis company on the other side of the country. This happened 18 months ago and brings us to today. I now work as the Director of Product Development for CannaCraft, located in northern California and one of the largest cannabis product manufacturers in the entire world! We’re very vertically integrated here at CannaCraft; meaning that we do everything from sourcing and growing cannabis, to extracting the cannabis oil from these plants, to using that oil to manufacture hundreds of various product SKUs (e.g. vapes, tincture/droppers, infused edibles, mints, beverages and many others), to doing our own distribution (as well as third-party distribution) delivering to dispensaries state-wide through our wholly-owned distribution entity KindHouse.

If you are a cannabis user living in California then you are most likely already familiar with some of our brands:

Care By Design: Care By Design is our CBD-focused, wellness brand. Founded in 2014 under the old medical cannabis regulations, it is the roots of what CannaCraft has become.

Absolute Xtracts: ABX’s target audience is more the recreational cannabis consumer. High-THC products that are formulated using strain-specific cannabis-derived terpenes.

Satori Chocolates: Our Satori brand is all about delicious infused chocolates and other edibles. We hired a culinary-trained pastry chef to make sure all of our edible confections taste fantastic. (and they really do!).

The Farmer & the Felon: This is our cannabis flower brand, for those consumer’s who enjoy consuming cannabis the old-fashioned way. The brand tells the interesting back-story behind CannaCraft’s co-founders Ned Fussel (the ‘Farmer’) and Dennis Hunter (the ‘Felon’).

Loud & Clear: Loud & Clear is a sister brand to ABX which focuses on high potency and flavor vape cartridges by formulating with live resin.

HiFi Hops: In a partnership with our friends down the road at Lagunitas Brewing Company we have created the best-selling cannabis beverage in California, which is the largest legal cannabis market in the world.

Want to see what goes on behind the scenes at CannaCraft? Let me take you on a virtual tour of our 30,000sq.ft. manufacturing facility located in Santa Rosa, California!

I'm here with you today for a few things!

First, I am excited to announce that we have just launched a brand new hemp CBD company Care By Design Hemp so for the first time ever we are able to legally ship the products we make over state lines, directly to people’s doors, almost anywhere in the US! For those who don’t know, hemp is a type of cannabis plant that produces only tiny amounts of THC, but most hemp is still able to make lots of CBD. Hemp has become federally legal under the 2018 Farm Bill, and so unlike the other products we make, we are able to offer these hemp-derived CBD products outside of California. This AMA intro is getting a bit long, so I’ll tell you all about what makes all our new hemp-derived CBD products cool and unique somewhere in a comment below. Though I do want to mention in this intro that we are giving out a hefty discount code to our online CBD store for all the Redditors taking part this AMA…enter promo code “CBDAMA30” for 30% off your entire purchase! We’ll leave this discount code active on the Care By Design Hemp website for the next 2 weeks or so.

Next, I can actually use YOUR help! I am in the midst of recruiting daily CBD users to take part in a current IRB-approved clinical study investigating the liver safety of using CBD products. Care By Design Hemp pooled funding with ten other prominent hemp CBD companies to fund this $1.5M+ clinical study to directly address the hepatotoxicity concerns expressed by the FDA. We are recruiting from all over the country, and if you participate in our study we will send you a free 3-month supply of a Care by Design Hemp CBD product of your choice, and you also get a $100 VISA gift card upon completion of the study! Participants will monitor their daily CBD use on a phone app over 30 days, then will go to your nearest lab testing center (e.g. Quest Diagnostics) to provide a single blood draw. Your blood will be analyzed for various markers of liver function and your results will be fully accessible to you! Some of the specific inclusion criteria for all study participants are that you can attest to 30 days of daily CBD use, and also have abstained from using any THC products in that time period. We only have around 100 spots left in the study, so if you’re a CBD user interested in helping to advance cannabinoid science and believe you might qualify, then take our online questionnaire here to go through all inclusion/exclusion criteria and sign up!

Lastly, you have a leading cannabis expert on the line here...Ask Me Anything! I’ve contributed dozens of presentations, peer-reviewed publications, podcasts, interviews and articles about cannabis and cannabinoids. As a long-time Ent (hi r/trees!) and lurker of Reddit I’m excited to be doing this! There are some things that I may not be able to touch on in order to protect company IP, but otherwise I’m an open book. AMA!

Proof!

Comments: 1669 • Responses: 35  • Date: 

Galileo009587 karma

While it's generally known that there is a line between cannabis use and overuse, what do you think is the upper limit of a reasonable amount to take? There's some debate over this, and factors like personal tolerance that make it more difficult to dicern, so I'm wondering where an expert and experienced user would draw the line at.

CByD_SciENTist_AMA1622 karma

Yes I agree there's a line between cannabis use and overuse, but I don't think it lends itself to saying that 'X-dose per week' is healthy and "Y-dose" is not. There are very real inter-person difference in how people experience the effects of cannabinoids. For example, I'm a tank and can take a 50mgTHC edible and remain fully functional, but my wife will have a near psychedelic experience if she takes even a 5mg dose...tolerance is part of it, but beyond that everyone is also so inherently different in how they process and experience cannabis.

In my view, overuse is when it begins to negatively impact other areas of your life. If you feel anxiety at the thought of not having weed for a day, it might be time to take a little break from it. I personally use cannabis daily and have since I was a teenager, but I mostly limit it to 'nighttime use' only after I have finished all of my responsibilities for the day. Even as a daily user I don't feel that I am over-using because I'm able to successfully take care of my life, work, financials, family and everything else. It's the 'wake and bake' and smoke 'all day every day' mentalities that lead to trouble for many people, and in my view there is less enjoyment of cannabis when being used that way.

DrHughHoney432 karma

As I've gotten older I've noticed that I don't do well with Sativas anymore. The strain tends to make me feel anxious and has even caused me to have panic attacks. I've heard this is fairly common with sativas... WHY????

CByD_SciENTist_AMA559 karma

Lots of things could be going on here. It's possible that your body could be processing the cannabis constituents a bit differently than you used to (especially if you take new medications or have gained/lost a lot of weight). Could just be a psychological phenomena. But if I had to take a guess, it's actually the flower that changes rather than you. What you used to use was simply less potent than what you get these days. Selective breeding has substantially increased average cannabinoid content of cannabis across the world and this difference is readily noticeable to people who have been smoking for a while. Good weed back in the 70s-80s was like 5%THC content, these days we have chemovars that are pushing 30%!

____willw____348 karma

How much do we know about the effects of cannabis, especially moderate usage, for teenagers, especially those that are 16-19 years old? Is this something we need to be really worried about? What effects might someone want to look out for at that age to see that it is having a negative effect? Also, should you wait to partake in cannabis until 25, or is the legal age a fine time to start, for your brain?

CByD_SciENTist_AMA574 karma

There's certainly still a lot we have left to learn about this. All I can say is that there has been some relatively negative data published on adult cognitive function when starting cannabis use too young. These same deficiencies were not observed in cohorts who started cannabis use later in life.

We really don't have enough data on this to say anything very conclusive, but I think it's safer to wait until you're an adult to begin consuming cannabis regularly. I started using cannabis when I was 14, but in hindsight that was probably too young!

Ganadote39 karma

We already know. Weed, unsurprisingly, is bad for your brain and lungs. The brain is still quite developing into your early 20s, but heavy users in their teens are at high risk to develop anxiety issues. DO NOT USE WEED TO TREAT CLINICAL ANXIETY.

Yeah, smoking every now and then likely won’t have any lasting health effects. Smoking everyday increases that chance significantly, which makes sense since you are altering the chemical makeup of you brain and putting a lot of shit into your lungs.

I really hope he doesn’t skip this question, because it’s so important and if he doesn’t acknowledge the health risks of smoking or consuming canaboids then he’s quite frankly a piece of shit who only wants your money. Hope he proves me wrong.

CByD_SciENTist_AMA39 karma

I'm not exactly following where we disagree here. My response acknowledged the health risk and was a recommendation to wait until you are an adult to begin use. Like you, I also do not condone the use of weed to treat clinical anxiety.

The vast majority of cannabis products we make and sell are not a smokeable form-factor so 'shit in your lungs' is not very applicable here. You rightfully shouldn't take my word at face value, I wouldn't in your shoes either, but I think assuming I'm a 'piece of shit who only wants your money' is a bit extreme.

Laserdollarz301 karma

Hi Matt. Some production chemist in the industry in Colorado, here. I hope this doesn't get buried under 100 other less-specific questions.

How much do you know about retention time of specifically nanoparticle THC in the body? In addition, similar to how antidepressants and other pharmaceuticals are detectable in public waterways, what kind of environmental effects might this incur? Is there a half life for sequestered cannabinoids (in the body, but far from enzymes)?

And last question: what's the most interesting paper regarding cannabis you have read in 2020?

Edit: 883 comments? Yea, this got buried. I'll pm you in a week and ask again haha

CByD_SciENTist_AMA115 karma

I see you now! Great questions.

When you say 'nanoparticle THC' I am going under the assumption that you are referring to emulsification technologies to create THC nanoemulsions, a tech that's fairly widely used in this space (though nanoparticle can technically mean some other things, so if you intended something else let me know).

Nanoemulsions are basically microscopic ~50-500nm diameter 'bubbles' of oil that we can entrap THC, CBD, or other hydrophobic (i.e. water-hating) compounds inside and allow them to behave in a way that is seemingly water-soluble. Like the oil and vinegar in your salad dressing, cannabinoids inherently do not mix with water. However, once emulsified we can make them stay suspended in water for years! Nanoemulsions are pretty simple really, all you need is a surfactant (lowers surface tension of water, like a soap) and an oil (we've used either olive oil or coconut oil), and technically some hardware to emulsify but that's getting off topic. Once these oil/soap/THC 'bubbles' form they will stay suspended in your infused beverage until you drink it, at which point the nano-bubbles will be absorbed and diverted to your liver for first-pass metabolism. Our digestion system is equipped to handle all kinds of foods we throw at it, including emulsions (in fact, milk is a naturally-occurring emulsion, though non a nanoemulsion it falls under the category of 'macroemulsion'). Our bodies break the emulsion bubbles down and processes the coconut oil molecules and the THC molecules independently. Once we get to that point in the liver the retention time is the basically the same as any other way you consume. However, emulsification greatly speeds the uptake time for the cannabinoids to be absorbed, and therefore is faster acting than traditional oil-solubilized edibles. If a drug starts faster, it also stops faster. People who consume cannabis beverages like our HiFi Hops will probably notice the effects 'hit' much faster and taper off faster compared to those times you ate a pot brownie. So the technical 'retention time' of THC in your body is the same, but nanoemulsions will help your body to begin processing them a bit quicker.

Next question was about the antidepressants and other drugs being found in water systems. I don't think we would ever see this type of problem with cannabinoids due to their lipophilic nature. Those other drugs are naturally water-soluble, so once they are in a major body of water it's very challenging to get them out. Cannabinoids don't 'want' to stay in water and will readily stick to pretty much anything in order to minimize its water exposure. Even emulsification would not only last a few years MAX before those 'nano-bubbles' merge with other oils they come into contact with.

Next question was cannabinoid half-life if sequestered away from away from enzymes. THC PK stuff is complicated, but all half-life figures you've seen already take this into account as THC readily sequesters to fatty tissue like adipose and brain. The canonical place for THC metabolic is the liver (but in reality there is at least some level of enzymatic activity in probably all tissues throughout your body). THC will sort of 'pop in and out' of the fatty tissue and into your blood at some rate. It is able to stay in the blood and get brought to the liver by binding proteins like HSA and some lipoproteins.

Most interesting paper I read in 2020...hmm...I love this one! (technically published December 30th, 2019..but I think that gets a pass). The group discovered a novel class of naturally occurring cannabinoids, THCP and CBDP! They are like THCV/CBDV, expect with 7-carbon alkyl chains instead of 3. Unlike THCV (which has CB1-antagonistic properties) THCP showed extremely high cannabimimetic activity in rodent models. No one has been able to isolate THCP in sufficient quantities for the market, but a few years and some savvy breeding, who knows?

Lotrent156 karma

Do you have any concerns/thoughts/insight into Cannabis Hyperemesis Syndrome (CHS)?

Longtime cannabis proponent here, and while we know it’s an order of magnitude safer than Alcohol, it’s still best to be responsible and not pretend it isn’t a drug that has potential to affect your body beyond a temporary effect.

Been reading about this topic some lately and while it sounds like it requires a heavy amount of sustained usage, it still seems like something we need to be made aware of in pop culture.

CByD_SciENTist_AMA132 karma

Yea CHS is an interesting phenomena that we don't fully understand yet. Cyclic vomiting that can be temporarily relieved by taking a hot shower. CHS seems to only happen in extremely heavy users, and has only recently become identified as a condition with the higher prevalence of concentrated oil preparations. Users abstain from cannabis do get better from it relatively quickly. It affects only a tiny fraction of heavy cannabis users (I don't know the numbers off-hand) so I think it might still be too rare of a thing to take much of a hold in pop culture. I look forward to following the research around CHS as it unfolds.

Ugnspannkaka154 karma

I saw a documentary about the cannabis industry in California and how the government has made it almost impossible to operate profitably as a small completely legal entity, so the big companies are coming in and wiping all the little guys out. Long-term, are the little guys screwed?

CByD_SciENTist_AMA183 karma

Good question! I think much of it will depend on how the regulations around cannabis develop over time. Right now it is extremely difficult for smaller players to operate successfully due to very high expenses (taxes, licenses, lab testing costs, etc) that are inherent to this industry and often nonsensical regulations that must be followed. Plenty of other challenges for smaller companies such as the cannabis industry not being eligible for any sort of federal aid (so no COVID small business bailouts, no federal grants or loans, etc). Things that other industries take for granted like simply having a bank account or applying for small business loans is also something that is largely unattainable in this industry, and more greatly impact the small guys.

I can see parallels between the alcohol industry and cannabis. The highly regulated nature of the product will lend itself to a small number of big players doing most of the manufacturing and distribution. BUT at the same time, there is room for craft breweries and things of that nature to exist too. On the agricultural-side I think there will be promise for small farms doing interesting selective breeding of cannabis chemovars that will appeal to the more savvy consumers and create a market for specialty strains. Dispensaries and things like cannabis lounges will become more prominent over time and can successfully operate more akin to a traditional 'mom and pop' shop.

Renfah8737 karma

This is exactly what I'm waiting for. As the market matures, competition will stiffen and margins will tighten. I'm envisioning the future of the industry is very similar where we have the giants like Budweiser and Coors, but also have a bustling craft scene. Hopefully over time some of these regulations and extremely high points of entry into the industry loosen so that the artisans can also go legal and put food on their table.

BTW, are you guys hiring? ;-)

CByD_SciENTist_AMA6 karma

Actually, yes! Here's a link to our 'Careers' page for a list of current job openings.

PicoRascar137 karma

Is there really a difference in highs between sativa and indica? People always tell me one is more uplifting while the other is more relaxing. I can't tell a difference after decades of trying and I find both are just as likely to be uplifting or relaxing.

CByD_SciENTist_AMA347 karma

Yes and no. 'Sativas' and 'Indicas' are terms that much of the cannabis community wants to start getting away from as they are sort of meaningless. The differences that people observe can most likely attributed to the different terpenes that are expressed by the cannabis plants. So the terpenes expressed by indica-like chemovars are generally believed to be more sedative, hence the couch-lock association. In reality, almost all cannabis you encounter today is really a sativa/indica hybrid due to so many generations of selective breeding. The terpene profiles are not always consistent between generations, which could lead to different experiences.

strudel_goblin132 karma

Are there any withdrawal effects of THC or CBD? Especially as it relates to anxiety (for example, with more alcohol use I’ve noticed higher anxiety levels in the days following)

CByD_SciENTist_AMA313 karma

I am not aware of withdrawal effects reported around CBD, even when using very high doses. However, heavy THC users who then abstain frequently report problems falling asleep and then experiencing very vivid dreams. This usually only last a couple days.

skarpelo65 karma

At what age would you recommend to be safe to start using recreational weed.?

Do you consider weed more or less dangerous than alcohol?

Do you recoomend using weed to people with conditions like
schizophrenia or depression?

CByD_SciENTist_AMA224 karma

I need to stay away from making medical recommendations, but I can say that there has been some relatively negative data on adult cognitive function when starting cannabis use too young. I think it's safer to wait until you're an adult to begin consuming cannabis regularly.

Alcohol is more dangerous...by a landslide....in pretty much every metric that has been measured. It's not even close.

Schizophrenics in particular often have adverse reactions to THC use so I would not recommend. Cannabis can probably be used sparingly by people with depression and some may find the effects helpful for them...but should not be used to TREAT depression! Talk to your doctor if your unsure!

-endjamin-51 karma

Are there any significant downsides to moderate daily use (i.e. nightly)?

CByD_SciENTist_AMA110 karma

Only you can answer that! Cannabinoids have a very high safety profile in a physical sense, but if cannabis use is negatively affecting other areas of your life then you might want to reassess. I personally use cannabis nightly and don't feel it negatively affects my life, but everyone is different.

wannabe_pineapple50 karma

How does smoking marijuana affect a feutus when a pregnant woman smokes it? Is it the same when the pregnant women eats it or uses oils?

CByD_SciENTist_AMA74 karma

I don't think we fully know for sure yet how negatively cannabis might impact a developing fetus...all I can say is that I would not recommend cannabis use while you are pregnant. This is a very challenging thing to study in humans (due to obviously ethical reasons around study design). I know there have been some observational studies on this in Jamaica that indicated a risk of decreased birth weight (though I understand that there are some criticisms of these studies for not controlling for concurrent tobacco use).

In any case, I think better to not risk it and totally abstain from use while pregnant and breastfeeding.

bubba999941 karma

I've read a lot of anecdotal stories about CBD's effectiveness for a variety of ailments. Are there any clinical studies that focus on medicinal uses for CBD for specific medical conditions?

CByD_SciENTist_AMA77 karma

Well, Epidiolex is CBD that has been FDA-approved to treat certain types of epilepsy. It's efficacy in this has been demonstrated beyond the shadow of a doubt. There's also a lot of promise for CBD in anxiety-reduction and as an anti-inflammatory.

Chemtorious40 karma

Hi Matt, first off thanks for doing this AMA, it's always exciting to hear from researchers in the Cannabis space!

What do you see as the most exciting/promising cannabinoid research happening at the moment? I see that your previous research was evaluating non-opioid pain treatment by modulating the endocannabinoid system; are there other areas of cannabis research with as much potential impact on medicine?

CByD_SciENTist_AMA48 karma

I think nearly all cannabis research going on now has that much potential! Historically it has been super challenging to do any research on cannabinoids due to federal prohibition. This led to us not knowing as much as we should about how cannabinoids are working and how they may be positioned as therapeutic options. What I find exciting is that there are more clinical trials than ever currently going on looking into the therapeutic efficacy of cannabinoid-based treatments, which is a huge and necessary step towards using cannabinoids in the clinic.

rmack1035 karma

Congratulations on living your dream job and being on the forefront of a rapidly growing industry!

I've been hearing a lot about terpenes lately. Could you give us a quick run down on a basic level of what is known about terpenes and maybe what is being studied at present?

CByD_SciENTist_AMA32 karma

Thank you! This really is my dream job and is an exciting industry to be part of.

Yes, I think terpenes are going to play a bigger and bigger role in the cannabis space over time. Terpenes are a class of compounds present in lots of plants. They are what's responsible for the taste and the distinctive odor of cannabis (cannabinoids themselves don't taste or smell like anything at all). They are believed to have various pharmacological properties (for example, the main difference between 'sativas' and 'indicas' is their terpene profiles...they make the same amount of cannabinoids on average), but there's precious little clinical research that's been done on terpenes so I cannot make any specific claims here that could be fully substantiated.

We try to harness the power of terpenes by formulating all our vapes with the terpenes we extract from the cannabis plant (many other companies will use botanical terpene isolates because it's much cheaper). For hemp products we can't legally ship cannabis-derived terpenes, however we found a way to utilize cannabis data to drive terpene formulations for our national Care By Design Hemp CBD formulations! We partnered with an Israeli research group who studied what cannabis terpenes medical patients blindly gravitated towards to treat their specific conditions, then did a comprehensive analysis of the commonalities between the terpenes of those chemovars and used those datasets to formulate our different products. I explained this terp research approach a bit better in this blog post I wrote recently, so check that out.

The_God_of_Abraham33 karma

Any thoughts on the safety of the various oil extraction techniques for vaping? AFAICT, CO2 extraction seems to be the least likely to leave nasty stuff in the oil.

CByD_SciENTist_AMA91 karma

If you are buying in California or other legal markets then it really doesn't matter much in terms of safety, as we are required to pay a third party laboratory to confirm totally safe levels of residual solvents. Anything you buy at a legal dispensary has already been extensively checked for safety. This information shown in a Certificate of Analysis (COA). COAs for all our products are freely given, for example here is the [COA page of one of our brand's websites](https://carebydesignhemp.com/pages/coa).

If you are buying on the black market I would advise staying away from hydrocarbon extracted oil (e.g. butane extraction). These solvents can be dangerous at even very low amounts, and there are literally no safety guidelines for people making this stuff in their garage. CO2 is considered the safest (as our bodies make loads of CO2 and it is a major constituent of the air we breath), however the startup costs of these systems is pricey so you don't often see this method on the black market. I think ethanol-based extractions are a safer bet on the black market, and better yet would be pressed rosins which are truly solventless extractions.

urinesain32 karma

My bachelor's is in biology, and I'm a partner in a b&m CBD health and wellness store where we focus very heavily on educating consumers. This question is probably more in depth than any customer would really need to know, but it's just been on my mind.

CBD is believed to lead to increased levels on anandamide (AEA). CBD doesn't bind directly to the CB1 receptor, but is believed to bind to an allosteric site on CB1 as a negative allosteric modulator, which is believed to be responsible for reducing the "high" associated with THC by reducing its binding affinity. I would assume it would have the same effect with anandamide? Is this perhaps how it leads to increased levels of AEA? Either through a feedback loop where the body notices that it isn't binding so it ramps up production? Or due to lack of binding it just naturally leads to increased levels of circulating AEA? Or is the increase in anandamide due to some other process?

I know I went more in depth in explaining my question than I needed to, as I know you already have vastly more knowledge than I do on the subject, but I figured if anyone else found my question interesting that it might benefit them having a bit more information on the background of what my questions pertained to. Also, if I'm wrong with any part of the above, I'd love to be corrected! Learning is probably my most favorite thing. Thank you for taking the time to do this AMA!

CByD_SciENTist_AMA29 karma

Wow I am impressed with this question! You obviously have a good amount of background knowledge on the subject to be able to conceive and articulate this question as well as you have.

Yes CBD is thought the be a NAM of CB1 with THC as an agonist, and I would assume probably affects anandamide binding modes to the receptor as well (but not necessarily). Though I doubt this is part of the underlying mechanism by which CBD is able to cause an increase in circulating anandamide levels. CBD is known to robustly inhibit FAAH (the enzyme that catabolizes AEA) activity in rodents and that's how we thought CBD was raising AEA levels (obviously blocking rate of degradation will increase the amounts elsewhere). HOWEVER, one of the most interesting research findings of my entire career was when we were experimenting with recombinant FAAH that we made from human, rat and mouse. CBD inhibited mouse and rat FAAH just as expected, but we did not see any inhibition of human FAAH! This led down a whole wormhole and I worked on identifying what made human FAAH less susceptible to inhibition by CBD. The research I'm talking about here was all published in this JBC paper, (Figures 3D,4,5,6,&7).

So it seems that rodents sharp anandamide increase is caused by direct inhibition of the AEA-metabolic enzyme, but in humans we think that CBD is competing for FABP uptake proteins upstream of FAAH. There is some question around whether competition at transport proteins is enough to fully result in this effect though, so there may be additional unknown factors at play here too (possibly even the one you suggested!).

JustPassingShhh27 karma

Do you see other countries waking up and legalizing it? I'm in the UK and openly honest that myself and my partner use weed. I have yet to find anything else that helps me so much. I have less anxiety, all my pain is muted to a manageable level or gone and i can socialize with ease. Also whats your favourite strain? Im fascinated by the strains, my fave is lemon haze, tastes so good

CByD_SciENTist_AMA48 karma

I'm still waiting for my own country to legalize it! We are in a very strange gray area where cannabis is operating legally at the state level, but 'illegaly' at the federal level. THC and even CBD (which is not psychoactive at all) are classified by the DEA as Schedule 1 drugs- by definition meaning they have 'no accepted medical value'...which is obviously just insane. To put it in context, cocaine is a Schedule II drug and thus deemed to be safer by the American government than CBD!

But YES, I do see the US and many other countries legalizing it in the next decade or so. There is just too much public support and positive clinical research data around it to ignore forever.

I'm with you on Lemon Haze..delicious! Been using a lot of Blue Dream recently and I'm growing some Jack Herer in my garden now that I also can't wait to try!

Sandgrease17 karma

Do you have any idea if using high CBD products can affect a person's tolerance or sensitivity to D9THC?

CByD_SciENTist_AMA49 karma

My personal belief is that THC and CBD are best consumed together. There's a bunch of research showing that CBD effectively reduces THC-induced anxiety. CBD generally mellows out the high of THC and most people find the combination to be more enjoyable than THC-alone.

It's a shame that it's become so difficult to find Type-II cannabis flower (i.e. mixed THC and CBD content) as the market pushes for the highest THC content possible, so most strains you see in the dispensary have mostly been selected AGAINST expression of meaningful amounts of CBD.

here4dambivalence14 karma

What are your thoughts, if any, on the current delta 8 scene and lack of enough oversight? Also what cannabinoids do you think show a much larger future interest for public knowledge and plausible consumption for anxiolytic or pain relief purposes? Thanks for your input, Dr. Weed.

CByD_SciENTist_AMA23 karma

I think the delta8 scene is going to change pretty drastically following an updated hemp guideline by the FDA published last week which lays out that formulating synthetic cannabinoids cannot define hemp. For those who don't know, delta8 is almost the same as 'regular delta9-THC, but has lower affinity for our cannabinoid receptors and thus exhibits about half of the psychotropic potency. Using some basic lab chemistry we are able to transform CBD into delta8-THC, which many people in the hemp industry were doing to allow them to ship a psychoactive cannabinoid over state lines. This conversion method of course makes the delta8 a synthetic cannabinoid, and thus will no longer be permitted under the 2018 Farm Bill. We sell a delta8 vape cartridge in CA under our ABX brand, but it is all plant-derived and is not hemp, so this updated regulation doesn't personally affect our business.

Unfortunately, cannabinoid research is still in it's infancy and there's still so much we don't know about many of the minor cannabinoids and their effects! However, there is placebo-controlled blinded clinical research demonstrating true anxiolytic effects of CBD. Also plenty of clinical research showing that THC is effective for treating mutiple types of chronic pain.

Thec0rn012 karma

Hi Matt! I have two questions

Is there any conclusive evidence for co-evolution between Homo sapiens and Cannabis sp.? I've read about the cannabinoids receptors on our brains, but I imagine those aren't necessarily specific for THC and/or CBD

On a more personal note, how does your family feel about you field of research and recreative use in general?

CByD_SciENTist_AMA37 karma

We evolved our endocannabinoid systems completely independently of cannabis. It is more 'luck' that the compound THC that the plant makes just so happens to 'fit just right' in our brain's CB1-receptors and thereby mimics the actions of our endocannabinoids like anandamide.

My mom was not too happy about catching me smoking weed when I was a kid, but she and everyone else is very supportive of my research interests and choices. She may be finding out the actual extent of my recreational use today during this AMA though lol.

MerDuck12 karma

How do you feel about CBD usage in animals? How much testing has been done? I know thc is toxic for them. My dog recently started having tremors and I don't know where to even begin to look for the proper amounts or quality for her. Any insight would be amazing. Thanks so much for letting us all pick your brain.

CByD_SciENTist_AMA26 karma

CBD is known to have anxiolytic and and anti-convulsant properties in rodents and humans, so I think it's likely to work similarly in other animals like dogs. I've heard lots of positive anecdotal reports from veterinary use of CBD, but there hasn't been enough controlled studies in non-rodent animals yet so I would run it by your vet before trying it.

THC isn't necessarily 'toxic' to dogs. However, unlike humans, canines have their motor coordination partially controlled by endocannabinoid system signaling, so they tend to get very 'wobbly'. Dogs are often frightened when consuming THC so I would definitely not recommend THC use.

rocketparrotlet11 karma

Are there any disorders associated with a dysfunctional endocannabinoid system?

Is there any way to up- or downregulate endocannabinoid production or receptor activation without using cannabis?

CByD_SciENTist_AMA15 karma

Look up 'endocannabinoid deficiency syndrome'. It's a theory largely pushed by Ethan Russo that some common disorders are rooted in insufficient levels of endocannabinoid signaling. This is really only a theory at this point and more research is needed to confirm.

The only way I know how to downregulate cannabinoid receptors is to use THC (or other cannabinoid receptor agonists). The only way to upregulate them is to abstain and take a T break!

Almighty_One11 karma

I worked with a P.I. at the Hauptman-Woodward Medical Research Institute about 10 years ago that was researching cannabinoids.

I remember him telling me it was damn near impossible for him to get Federal research funds. Do you run into the same problems getting grants?

I don't remember what exactly his field of study was, but our facility performed x-ray crystallography. Even with something so minor, he always ran into problems getting grants.

CByD_SciENTist_AMA18 karma

YES this is a big problem. My lab in grad school had a DEA license to carry Schedule I drugs, which allowed us to write some successful grants involving cannabinoid research, but this is a big regulatory burden for a lab and not something most people have access to.

I think cannabis is being less stigmatized these days which will help grant review processes, but there are still loads of hurdles to overcome due to the federal Schedule I status of cannabinoids.

Ansem_T10 karma

QC Scientist here with background in Pharmaceuticals. How do you set QC standards for impurities/quality? I would assume since Cannabis isn't federally legal, you can't use federal regulations for quality limits (aka FDA/USP type guidelines). Are these tests done in-house, or do you mainly use an outside lab?

Also, do you use GMP for your Cannabis production lines? Or is it more akin to a bakery/food service?

CByD_SciENTist_AMA13 karma

Yea it's a weird place where the cannabis industry is makes consumable products while not being at all under the purview of the FDA. Even though the FDA does not oversee us, we still optionally abide by FDA guidelines for all our products and processes.

Many QC impurities are mandated by the state to be quantified by a third party lab during Phase III compliance testing, which results in a COA showing a clean bill of health for potency, residual solvents, microbial contamination, mycotoxins, and heavy metals (here are where we post our hemp COAs to see an example).

Check out the 'virtual tour' video I posted in the intro to get a general idea of what our facility is like. It's not really at all like a bakery.

asher9210 karma

Any tips for a soon to be PhD in molecular bio to get started in the cannabis science industry? In Northern California.

Edit: a word

CByD_SciENTist_AMA7 karma

It depends on what aspect of the industry you want to go into! Cannabis lab testing is a growing field and has a demand for scientists, so becoming proficient with common analytic techniques used (e.g. LC-MS, GC-MS, PCR, ICP-MS) would look good on an application.

The cannabis industry wasn't even really a thing when I started grad school in 2012, so it's obviously not something I was aiming for from the get-go. I just had selected to attend the MCB PhD program at Stony Brook and fell into researching cannabinoids (more precisely, protein-mediated intracellular transport mechanisms of cannabinoids and other bioactive lipids) through a combination of interest and luck. If you have enough interest and luck you can follow a similar path as me and have a research focus that is somehow relevant to cannabinoids. It's a critically under-researched field and there's so much 'low-hanging fruit' for research projects and grant applications!

DylanVincent8 karma

Have you ever watched The Big Lebowski...on weed?

CByD_SciENTist_AMA12 karma

Only 20 or 30 times.

FLINTMurdaMitn8 karma

Why do people keep producing high THC / low CBD strains? From my understanding this is not the best for your mental health as the plant naturally has a balance between the two. Basically we are creating a higher probability of adverse reactions when this is done. Why wouldn't we beable to produce a plant with higher amounts of both to counteract the bad reactions. I get it, people want to get super high but in all actuality by doing this we are taking out the balance and creating a problem. Also anytime we do this we creat a sever problem with any "drug", just look at cocaine and crack and opium and heroin. The coca leaf in itself is a non problematic plant alone, as soon as we concentrate it then a problem occurs, the poppy plant is almost the same.

CByD_SciENTist_AMA8 karma

The simple answer is that the market drives it. The typical dispensary consumer is looking to get maximum amounts of THC per buck they spend. Most people just want to see high numbers in the THC category, which means lower numbers in CBD.

THC and CBD both are derived from CBG, so maximizing the amount of one necessarily reduces the amount of the other. If you want try to breed a cannabis plant that produces flowers with an extremely high 30%THC content, it will certainly have almost no CBD mixed in with it, essentially because all of the CBG went towards making THC rather than CBD. You could never have a plant with 30%THC content and 30%CBD content, and the ones that we can realistically grow like 15%THC+15%CBD tend to not sell well because the average consumer perceives "15%" as being a low potency number.

I personally find a mixed THC/CBD profile (i.e. Type-II cannabis) to have the best effects, so it's sad that it's becoming so hard to find. Almost everything these days seems to be either hemp or all THC! I'd take a lower potency, mixed cannabinoid profile product any day.

Tide_2_go6 karma

What can you tell me about delta 8 thc?

CByD_SciENTist_AMA7 karma

It's a natural isomer of regular delta9-THC. The molecule is almost completely identical, except for the position of one double bond.

Delta8 exhibits about half the affinity as delta9 towards our CB1 receptors, and this results in a relatively more mild 'high'.

I think delta8 will be showing up in the news more over the next couple months as the result of a new update from the FDA that was published last week, banning synthetic cannabinoids from defining hemp. We are able to convert regular CBD into delta8 with some simple lab chemistry, and some hemp companies were doing this as means of shipping a psychoactive substance over state lines. This CBD->d8-THC conversion makes it a synthetic cannabinoid, and therefore will no longer be allowed in the hemp CBD market.

neuromorph5 karma

How do you feel about those incarcerated for what you can freely do now?

CByD_SciENTist_AMA5 karma

Yes it's absolutely insane to think about. The cannabis industry was deemed an ESSENTIAL business during COVID, yet simultaneously there are thousands of people sitting in a jail cell for possession offenses! It's so backwards and sad.

We contribute part of the proceeds from our Farmer and Felon brand to support the Last Prisoner Project, which is an organization based on freeing these unfortunate individuals. It's something we can do at least...

ThirdWaveSutras2 karma

Can we get a low thc product? People just want to chill not go to the moon.

CByD_SciENTist_AMA2 karma

Yes! That's what our Care By Design brand is all about!! We created the 'Ratio approach' to dosing so that people can tailor their THC intake to what's most comfortable for them. Each 'Ratio' product is simply a ratio of its CBD:THC content (for example, a 2:1 product might contain 100mgCBD+50mgTHC).

We currently make our in-state Care By Design products in 1:1, 2:1, 4:1, 8:1, 18:1, and 40:1 ratios. If you want even less THC than that, you can use the 30%off promo code I gave out in the intro above to try some of our Care By Design Hemp CBD products. As we believe in a full-spectrum approach, even our hemp stuff contains a tiny bit of THC! (the amount varies by batch, but usually it's about 1mgTHC/mL or 1mgTHC per softgel...not enough for most users to feel anything from it at all).

TranquilSeaOtter1 karma

Who's lab did you work in while at Stony Brook? Did you also call it Stoner Brook?

Did you ever think about the endocannabinoid receptors in the gut and if those receptors are activated when someone ingests cannabis? I know there are receptors there but I'm just not sure to what degree those receptors are activated and what the downstream effects are.

CByD_SciENTist_AMA1 karma

I was mentored by Drs. Dale Deutsch and Martin Kaczocha at Stoner Brook.

Yes there are CB2 receptors present throughout the GI and consuming cannabinoids likely activates them to some extent. We don't have enough data yet to substantiate this for any GI disorders, but this is something that is actively being researched now!

blitztein--1 karma

Did you get high on your own supply tho?

CByD_SciENTist_AMA2 karma

Yes