Marijuana is a very complex plant: many different strains with differing profiles of psychoactive, non-psychoactive, and peripherally-active compounds that impact metabolism.  Most have THC, which activates endogenous cannabinoid receptors and mimics many of the effects of smoked marijuana (eg, see studies by Hart, Wachtel, and Curran).

Do not underestimate the complexity of this plant.





I’m not ‘anti-pot’ as there are far worse drugs out there… however, some advocates make really bad “pro” arguments, like saying it’s actually healthy (or at least not harmful in any way)…
there are many independent lines of evidence which suggest otherwise, metabolically speaking.


MJ not crack


Rimonabant, the notorious pot-blocker, reduces appetite and is a fairly effective weight loss drug, but has the unfortunate side effect of doing the opposite of marijuana, psychologically speaking.  See any of the RIO studies, eg:


weight loss Rimonabant


All participants lost weight and experienced improved metabolic profiles, insulin sensitivity, etc., by blocking endogenous cannabinoid receptors.

Adverse effects?  Wellll, there’s a drug called Marinol (pure THC) that’s technically an anti-emetic (reduces the urge to vomit); it improves appetite in patients with conditions associated with anorexia or wasting.  It’s a cannabinoid agonist.  Blocking CB1 with Rimonabant induces nausea in some patients: no bueno, but not unexpected given the known effects of Marinol.  Rimonabant is also associated with depression and anxiety (in some patients); also not unexpected.

So, it’s not a good idea to block this receptor pharmacologically (for psychological reasons) or activate it recreationally (for metabolic reasons).  Obesity researchers (and big pharma no doubt) are still looking for a pot-blocker that doesn’t penetrate the brain  to avoid the negative psychological side effects (eg, Klumpers et al., 2013).



Best. Graph. Ever.  The effect of Rimonabant on how stoned participants felt after smoking pot.  Yes, “Stoned” was published in the Journal of the American Medical Association (Huestis et al., 2001).




Indeed, Rimonabant effectively treats “cannabis intoxication” (Crippa et al., 2012).  Antagonist versus agonist 101.


Part II: the biological effects of cannabis, THC, marijuana, and antagonists, etc.


THC acts like insulin on adipocytes: increased adipogenesis, fatty acid uptake, and decreased lipolysis (eg, see studies by Teixeira and Cota).   Munchies, anyone?

Cannabinoids and mimetics/agonists induce hunger and repress satiety; cannabinoid blockers induce satiety and weight loss.  However, I actually don’t think marijuana is obesogenic aside from its anti-anorexic effects.  Cannabis use is not always associated with obesity, possibly due to confounding and/or the lack of good crossover studies (you can’t really do a proper study in healthy humans with MJ for ethical reasons).  But most rodent studies agree that cannabinoids, acting via cannabinoid receptors, induce metabolic syndrome-like effects in nearly every single tissue and on the whole-body level.



CB1 cannabinoid receptor deletion in mice leads to leanness, resistance to diet-induced obesity, and enhanced leptin sensitivity (Trillou et al., 2003).  For context, mice lacking CB1 is somewhat analogous to humans not smoking marijuana.

In liver, cannabinoid signaling induces fat accumulation and insulin resistance (Osei-Hyiaman et al., 2008).  This is absent in CB1 and liver-specific CB1 knockout models.   Mice overexpressing this receptor in liver exhibit increased insulin resistance (Liu et al., 2012).

Activating cannabinoid receptor-2 (CB2) causes insulin resistance and adipose tissue inflammation, and this is blunted in mice lacking CB2 (Deveaux et al., 2009).




The knockouts & over-expressing rodent models, and pharmacological agonist & antagonist studies are all consistent.  That said, I still don’t think this is the worst recreational drug out there, even among “legal” ones.



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  • bradjkovacs

    Did any of the literature you read mention the duration of the negative metabolic effects of activating CB1/2? I use marijuana to sleep but don’t eat once I’m smoking. If I’m not smoking during the day, would my insulin sensitivity, leptin milieu, etc., be working properly or would I still be impaired?

    • THC has a half-life > 24 hours, so a better question might be relevant concentrations and binding affinities… which I don’t know.
      Theoretically, daily use could result in chronic CB signalling, but this might not matter if, for example, low dose.

  • rs711

    Ah, you made my day Bill, so much nicer to see a train of thought rather than claims of ‘delusion’ hehe! 🙂

    Those who think marijuana is devoid of side-effects/downsides are either hippies or ignorant.

    For the record I don’t assume you’re anti-pot but I do think you’re wrong about cannabis pushing someone towards MetSyn.

    Good on you for recognizing “Do not underestimate the complexity of this plant”.

    Opening the links of the studies you cited, most (I didn’t count) use THC, CB1/2r ant/agonists & synthetic mimetics in isolation in addition to receptor KO models. That’s all pretty normal/standard, seeing as it’s the usual step-wise process of assessing receptor-by-receptor effects, establishing dose response curves etc… What I don’t agree with is the (seemingly) straight line extrapolation you draw from these isolated compounds in vitro or in rats to humans when humans (nearly) always use whole-plant buds & extracts. We’re now comparing apples with oranges. For one, these studies entirely ignore (control for?) the effects of the many terpenes present in the plant. Secondly, Marinol is not a particularly good drug as a majority of patients who are prescribed it will tell you. They opt for the buds or extracts because, for example, CBD moderates the high of THC. CBD is an anti-psychotic (in addition to tons of other things it does). I would not advise someone take THC alone as it’s quite unpleasant apparently.

    You say “All participants lost weight and experienced improved metabolic profiles, insulin sensitivity, etc., by blocking endogenous cannabinoid receptors.”
    Correct me if I’m wrong but the assumption is that an agonist would produce the mirror effect (gain weight, worsen metabolic profile, increase IR etc), right? Well, it’s just that – an assumption. Observational data lends us a hand here, essentially discrediting this causal relationship you seem to be postulating TL;DR “We found that marijuana use was associated with lower levels of fasting insulin and HOMA-IR, and smaller waist circumference.” Epi-studies can’t prove causation but they can sure disprove it 🙂 ..of course, assuming the data & statistic aren’t total crap hehe.

    A few studies you cite are funded by NIDA which as you may know, is given the directive to show HARM in the substances it investigates – not to investigate any & all effects. This of course, is symptomatic of a profoundly broken application of the scientific method.

    Look at this (yes, in vitro) study which is a counter-e.g. of pot contributing to MetSyn. Actually, quite the opposite. “The Stimulation of Ketogenesis by Cannabinoids in Cultured Astrocytes De?nes Carnitine Palmitoyltransferase I as a New Ceramide-Activated Enzyme”

    Authors note: “The activation of CPT-I by cannabinoids in astrocyte cultures was concomitant with a quantitatively similar stimulation of ketogenesis from palmitate. This is consistent with recent determinations of flux control coefficients of the enzymes involved in long-chain fatty acid oxidation, which show that CPT-I catalyzes the pace- setting step of ketogenesis in astrocytes and hepatocytes. In addition to CPT-I, mitochondrial HMG-CoA synthase has been suggested to be a putative important site of control of ketogenesis from acetyl-CoA in astrocytes and hepatocytes. However, in the present study the THC-evoked stimulation of ketogenesis from palmitate was not ac- companied by any change in mitochondrial HMG-CoA synthase activity. In addition, THC had no effect on ketogenesis from octanoate. Hence, the regulation of astroglial ketogenesis by THC seems to be independent of HMG-CoA synthase.”

    Or “Cannabidiol arrests onset of autoimmune diabetes in NOD mice”
    Or “Cannabinoids: potential anticancer agents.”

    How to explain Tashkin’s observations about smoking cannabis, COPD & lung cancer? Why the hell isn’t it messing everything up? Surprising really.

    Cannabis is such a potent anti-inflammatory agent that arguing that it pushes humans towards a MetSyn phenotype is wrong in all likelihood. Can we construct isolated examples in certain models? Sure! But can we then make a generalized statement about that sort of effect on humans? Clearly, no.

    I’m actually quite interested in discussing its downsides, like for example, it’s effect on alpha-wave potentiation which, depending on the kind of learning one is engaging in is probably not a good idea.

    It’s funny I’m here ‘defending’ it because I often advise people against using it or using it very differently than your typical recreational stoner. I will admit though that it’s a class of compounds & system to which I’m endeared lol. We all have our favorites.

    I’ve got much more data to share and am happy to make an effort find data arguing against its use for specific cases…if you’re interested. Something tells me that may not be the case 😉


    PS: all links I shared I’ve read

    • bradjkovacs

      I’d be interested in your data/papers if you’d be willing to share. Thanks.

      • rs711

        Find me on twitter @raphaels7 or by email ( & i’ll send you some screenshots of various papers or papers themselves.

        I’ve got no data of my own to speak of 🙂 …except my anecdotal experiences.

    • “Correct me if I’m wrong but the assumption is that an agonist would
      produce the mirror effect”

      Antagonist: rimonabant = ?appetite, ?nausea, etc.

      Agonists: marinol & MJ = ?appetite, ?nausea, etc.

      Same effect observed with knockout and transgenic animal models…it rarely works out so clean-cut with other receptors

      • rs711

        Got it.

        The issue is not grouping Marinol & MJ as agonists (clearly they are). The issue is assuming they’re essentially equivalent (clearly not, for the following reason). For e.g., the decrease in nausea with MJ is more effective than with Marinol alone & comes with fewer unpleasant psychotropic side-effects (MJ is very pleasurable to some patients, obviously). How they modulate their effect is similar but with markedly different outcomes as far as patients are concerned. Aren’t end-point markers like patient reports & treatment outcomes above surrogate ones like in vitro phenotypes in the hierarchy of evidence? We want to have data on both but, I think, recognize which one we’re aiming for (end-point markers).

        • word.
          I’ve heard this too, patients prefer cannabis over Marinol. Not surprised.

          I still make generalizations (maybe wrongly) about “consistency” because, for example, Rimonabant makes people feel less “stoned” after smoking pot, treats “cannabis toxicity,” and reduces appetite,
          suggesting THC is one of the major compounds in cannabis mediating these effects via CB receptor. All of the predicted effects are there, no surprises.

          “in vitro phenotypes?”
          all of the mouse data agree as well (agonist/antagonist, transgenic/knockout, etc.)

          • rs711

            MJ FTW 🙂

            For something to be truly toxic there must be an LD50 that can be achieved and you simply can’t physically smoke enough cannabis to die of cannabis intoxication. You’d die choked from the smoke (no oxygen) before the cannabis would kill you LOL!

            All this to say that, what I guess they’re referring to is simply doing away with the high. That being ‘high’ fits under the umbrella of ‘intoxication’ (like for alcohol) is a whole other story hehe…

            As for the in vitro phenotypes I’ve provided some examples where cannabinoids produce desirable phenotypical changes &/or changes in disease end-points (not sure if I’ve provided cancer data in mice here but there’s quite a bit out there)

        • Michael Trumper

          Had treatment for a non Hodgkins lymphoma many years ago and was actually advised by my onocologist to use the “real thing”, but to defer to my parents I got a prescription of Marinol. As I later told anyone who was willing to listen, it had all the bad effects and none of the good effects of the plant. Needless to say, I quickly abandoned it. Needless to say, because I was buying unregulated street drugs the cannabis I did have varied greatly in its effectiveness. I now know that it is the interaction or blend of THC and other cannibinoids that provides the desired effect.

    • these mouse models are actually pretty good for testing pro/anti-inflammatory pathways on insulin sensitivity — I’ve done this in the lab for many years.

      CB signaling consistently impairs insulin sensitivity across the board. Consistently.
      If there was a hint of “potent anti-inflammatory,” we’d see it in at least one of these models, right? (agonist, antagonist, knockout, transgenic)

      Maybe (hopefully?) there are other compounds in the whole plant which negate the detrimental effects of CB signaling,
      because from where I’m sitting, excess CB = no bueno.

      • rs711

        ‘excess’ anything is by definition detrimental. I have no issue accepting that inflammatory markers arise from CB1 (or CB2?) receptor over-activation in isolation – but again, that’s simply not what we’re dealing with in whole plant extracts. It’s good to know what these compounds do in isolation but it’s a big mistake to assume ‘that’s how the plant works too’. It’s analogous to not eating a certain plant only because a bitter compounds is poisonous in high doses in isolation.

        If this inflammatory phenotype is so consistent, why does it have such a long medical medical history (& success, I think) in treating inflammatory conditions? Do you think these patients & practitioners are either wrong or actually harming themselves? (I’m not being facetious – genuinely curious).

        ‘Cannabis anti-inflammatory’ in PubMed gives an extensive list of studies (at different stages & of different types) supporting a strong anti-inflammatory effect. Not ALWAYS, granted. But again, that’s not a shocker hehe. I’m surprised that you say this effect is so consistent though, as just plucking a few out of the hat gives:

        -“Cannabinoid receptor type 2 activation induces a microglial anti-inflammatory phenotype and reduces migration via MKP induction and ERK dephosphorylation” (haven’t read)

        – “Cannabis-based medicine reduces multiple pathological processes in A?PP/PS1 mice” (haven’t read)

        – “Cannabinoid receptor type 2, but not type 1, is up-regulated in peripheral blood mononuclear cells of children affected by autistic disorders” (have read)

        I *think* you may be approaching CB1/2receptors from too singular an angle. There’s a lot of data to the contrary and a few epidemiological studies not showing a MetSyn / inflammatory phenotype at all (suggesting the opposite – but which we can’t use as evidence for of course).

        • “‘excess’ anything is by definition detrimental”

          Good point. I should’ve said something along the lines of ‘exogenous’

        • “why does it have such a long medical medical history of success?”

          1) speculating here, but possibly due to how it’s used in practice: it will help people sleep, chill out, etc. Maybe even muscle relaxant effects?!


          2) I don’t think it’s acutely very harmful at all (there are many MANY worse drugs out there)

    • “It’s funny I’m here ‘defending’ it…”

      no, I was quite expecting you to come out in full force defending it! and you didn’t disappoint 🙂

  • Tuck

    No anandamide?

    • there are a couple known endogenous cannabinoids

  • rs711

    Another point worth noting is about increased appetite.

    Exercise stimulates appetite yet we don’t make the link with it making people obese, really (and we know calorie expenditure during exercise doesn’t usually make people less obese – not for long at least). So even if cannabis stimulates appetite, it doesn’t appear to mess with fat mass homeostasis as anecdotally & from epidemiology, adjustment in subsequent food intake follows normally (i.e. reduced calories).

    However, we do live in a junk food society. And the more junk food one is prompted to eat, the worse. So, that is a problem. But then, people who exercise a lot and fill up on junk food afterwards also has issues. I’m making the analogy between cannabis and exercise but am not pretending they’re equivalent hehe! (just my ‘not crazy’ disclaimer lol)

    • agree — I view cannabis more as anti-anorexic, not particularly obesogenic. The mouse studies are mixed on this point, but I still don’t come away thinking weight gain.

  • Reversible and regionally selective downregulation of brain cannabinoid CB1 receptors in chronic daily cannabis smokers

    yet Rimonabant still works… see study by Huestis: decreased “Stoned” feeling after toking

    • rs711

      i think that’s to be expected. question is, what does it mean? I don’t know

      • “downregulation of CB1 receptors”

        maybe this occurs in a region of the brain *not* involved in getting high?

        or it just doesn’t matter; ie, downregulated but still enough left to send the signal

        • rs711

          i’d assume it’s the CB1r that downregulate but…could it be something else?

          Regardless, there’s tolerance that builds up to cannabis but it’s not exactly comparable to that of cocaine, heroin or alcohol. a daily stoner will still get very stoned but will need more to get there. however, some people will take shit-tons of coke and just won’t reach that same high. cannabis tolerance is also easily reset (a few days or week or 2). i have NO IDEA what mediates this difference between cannabis & other classic drugs but it’s really interesting.

          • “cannabis tolerance is also easily reset (a few days or week or 2)”

            Given the half-life of CBs and their potential to be stored in adipocytes, I’d be surprised if it was on the scale of days… but your experience may trump my guessing in this regard 🙂

          • rs711

            oh no doubt about that…it really is a matter of days typically & for some people 1 week or 2 at most.

            it’s such a pronounced effect that, for e.g., say you go on vacation for a few days and don’t smoke, you either:

            a) are careful not to smoke too much the night or 2 without letting it settle in (if you’re looking to moderate the high) or…

            b) use the ‘reset’ tolerance to get wwaaayyy high on very little lol

            to each his own 🙂

          • rs711

            trace cannabinoids stay in adipocytes for a few weeks (maybe a few months) but it’ll stay in your hair for aaggeess (many many months).

            important to know this if you’re drug tested for work &/or for driving laws hehe

  • Colin P. Müller


    – Every pothead ever

    Sorry but marijuana is still a shit drug, mainly abused by dickheads.

    • rs711

      Thanks for your valuable comment. It has enriched us all.

      • Colin P. Müller

        Weed is a garbage drug. I rather do alcohol or opiates.

        • rs711

          Again, thanks for your valuable comment. It has enriched us all.

  • “Cannabis and Cannabinoids” — pros & cons, very interesting:

  • Cannabinoids and cancer: pros and cons of an antitumour strategy

    • Nagar J

      Bill, how do you square your statement

      “…cannabinoids, acting via cannabinoid receptors, induce metabolic syndrome-like effects in nearly every single tissue and on the whole-body level.”

      with the apparent anti-cancer effects of those cannabinoids? Don’t “metabolic syndrome-like effects” seem to *promote* cancer?


      • pure speculation: the pathways look very interesting, but much of the success of CBs in cancer therapy seem to be via improved appetite and shifting metabolism toward the “fed state.”
        This disconnects with the activation of a “fasted state” metabolism via CBs in cell culture.
        In other words, CBs may work in vitro, but the effects may be cancelled out in vivo where the therapeutic effect is increased food intake.

        honestly, not sure though. Just speculating

        • rs711

          i strongly doubt cannabis will ever be a stand alone for cancer. i doubt anything will ever be a stand alone for it.

          even now, we’re seeing ketones + HBOT + ketogenic diet or radiation therapy + ketogenic diet…i think cannabis could be added to either regiment but HOW & in what capacity exactly can’t currently be answer AFAIK.

          the “in vivo cancelled out” is a real concern. even things which can work alone could, plausibly, counter-act each other. they could also synergize. only way to know is to test. with the US leading the way in cannabis reform that could soon become a reality – fingers crossed!

          • This Old Housewife

            Especially since cancer can become treatment-resistant, and shift it’s defenses. Cut off the source of fuel, however….THERE’S your stand-alone treatment–a keto diet.

  • Cannabinoids inhibit energetic metabolism and induce AMPK-dependent autophagy in cancer cells

    • rs711

      putatively, autophagy via AMPK signalling is really cool for handling cancer cells. Their RTG response is bypassed & so they don’t apoptose. It’s hypothesized that endo or endocannabinoids can also induce apoptosis via – maybe pushing metabolism through ox. phos rather than substrate level phosph or glutamine fermentation. or maybe ceramide signaling? who knows…but it’s cancer battling effects are pretty strong. i doubt that whole plant extracts, at least from current strains, are sufficient alone to make much of a difference. topical applications of CBD oil might be an exception but the data is still too anecdotal so far. I hope they explore that further because it’s quite promising (anecdotally & in theory)

  • Autophagy, Warburg, and Warburg Reverse Effects in Human Cancer:

  • Ela

    So, where do we get rimonabant? 🙂
    I’m puzzled a little by this, although what I’m about to say is probably covered by your opening remarks about MJ’s complexity.
    My impression has generally been that MJ amplifies how a person tends to be already. So, if someone tends to be relax/munchy, it makes them more so. If someone tends to be anorexia/paranoid, more so. Mostly from observing myself but others too.
    So, my n=1: aside from not liking that I could feel it in my system for a week after using, I couldn’t become a regular user bc I became even more paranoid and appetite-suppressed than I am anyway. (I think I got the munchies maybe twice ever). One time ingesting => psychotic & paralyzed simultaneously, which was fun but scary.

    This is why I love working with plants so much–impossibly ramified variables. Is this telling about my own weird chemistry, or about the chemistry of the different MJs I’ve experienced in different places and times (UK, CA, HI, AK, never regularly/consistently and not in the past 7 years)…

    • rs711

      i wouldn’t touch Rimonabant with a 10ft pole. But if psychosis, GI distress & tons of other tortuous effects seem alluring…….lol

      • check out the subgroup analyses in RIO. The drug was safe & effective in many participants — no apparent side effects.
        Not sure exactly why.

        • rs711

          hhhmmm, i don’t see it in quite that positive a light.

          1) ITT numbers given not NNT – not too sure what can be made from that.

          2) “All patients received daily treatment with
          rimonabant (5 or 20 mg) or placebo for 1 year plus a hypocaloric diet (600 kcal/day deficit) and
          advice on increased physical activity”
          – I think the 600 kcal/day diet is a big ass confounder. maybe fasting diabetics & the obese mitigates MetSyn &/or psy disorders? (wouldn’t be the first time this is suggested…)

          3) Even if we trust their regression analysis saying 45-57% of the effects can be attributed to Rimonabant then that’s still not saying much at all..dismal consider 4)

          4) “[side effects] gastrointestinal, neurological, and psychiatric
          in nature. Serious adverse events were infrequent and almost equivalent to placebo. Overall discontinuation rates were similar across
          treatment groups, except discontinuation
          from adverse events, which occurred more frequently with 20 mg rimonabant versus placebo (most commonly, depressive disorders
          [1.9 vs. 0.8%], nausea [1.4 vs. 0.1%], mood alterations with depressive symptoms [1.0 vs. 0.6%], and anxiety [1.0 vs. 0.3%]). A thorough review of psychiatric and neurological
          adverse events was performed.”
          – IMO, if something increases rates of psychiatric disorders to treat obesity & diabetes then that’s a terrible drug, since these 2 diseases are things we can treat very well with nearly no side effects (or at least, with a much better cost-benefit analysis than rimonabant).

          I don’t have the data under hand right now but I remember reading about how the effects – especially psychiatric ones – were actually much more severe than reported here. I’ll try to dig it up.

      • Ela

        I do psychosis/gi distress/etc. already. But having gained weight in April over 90lbs for 1st time in couple year using supposedly a fat-binder, I’m desperate & willing to try any substance!

        • rs711

          i’m no doctor, so take it for it’s worth but…i strongly recommend you don’t seek out rimonabant (not even sure it’s widely available anyways).

          Bill & others have written about other, safer and more effective interventions.

          • Ela

            No worries! Having good effects right now w a diet pill+unbelievable amts of caffeine (dunno how a 90lb body can process it, having been unable in past). Also extreme nausea>app suppression, brought back from point of unbearable with just a little sea salt–interesting.

        • donny

          All of these can get worse. The closer you are to the edge, the less it might take to push you over. I’ve done psychosis. Not to be messed with.

          • Ela

            it’s true. btdt, i agree. living in AZ instead of AK (so better circadian regulation) has done huge things for avoiding psychosis. but too much food-restriction/too many diet pills/electrolyte imbalances from extreme heat & you can do it here too.

  • donny

    Anti-anorexic could still be fattening, depending on the conditions going in, though. In a permissive rather than causual sense. This whole thing makes me think of the studies with omega 6 fatty acids and rodents. Feed a high fat diet, at 1 percent omega 6, it’s not fattening. At 8 percent, it is. The same is true of a moderate fat or a low fat diet at those two percentages. This throws into doubt the idea that the high fat diet is fattening because of fat per se.

    The researchers blame endocannabinoids ultimately formed from products of linoleic acid for this effect. So–excess omega 6, excess cannabinoid, obesity. A problem with this is that these are rodents, in a cage, eating bland chow all of their lives. No natural sunlight, never a green herb, no morning dew tickling their bellies, or whatever it is that wild mice get their pleasure in life from. So, does 8 percent linoleic acid cause excess endocannabinoid synthesis? Or does it help these animals to self-medicate with food? Eight percent linoleic acid might be high, but I think 1 percent might be a little hard to do by accident in nature. So are cannabinoids abnormally high with 8 percent, or abnormally low at 1?

    • Although it’s probably not totally accurate, NHANES puts us somewhere in between, around 4% or so of calories from linoleate. And we obviously have a weight problem, so if this is the cause (I don’t think so, too oversimplified), then 4% would be too high and 8% way too high.

      • Jack Kruse

        Two ways to skin this cat Bill…….it is really an excess of omega 6’s or maybe a serious deficiency of 3’s in the CNS? I think the latter……….BOOM. Why? Patient who use weed under my cares top using when I get them eating seafood……and their drive for weed for sleep and pain drop too. Biology is not linear… is far from equilibrium.

        • Ted r

          Jack I’ve recently noticed a stark contrast in desire for Cannabis after just days of increased seafood and DHA.

          Being in the cannabis industry myself I’ve been to numerous seminars on Clinical Endocannabinoid Deficiency ( with the thought from the very beginning that this sounds like Omega acid imbalances. As endocannabinoids are metabolically derived from these fats yet virtually no one talks about that aspect.

          I view medical cannabinoid therapy as band-aids for underlying diet and light issues.

          If anything I view exogenous cannabinoids as helpful in transitioning metabolic states. I’ve witnessing first hand the benefits for cancer and epileptic patients so I do know it has application.

      • rs711

        that’s right, 4% is too damn high.

        can’t find the exact numbers for omega-6s for humans but Masterjohn says “The true requirement for EFA during growth & development is less than 0.5 percent of calories when supplied by most animal fats & less than 0.12 percent of calories when supplied by liver” – ‘How Essential Are the Essential Fatty Acids?’

      • donny

        Ya, but are there studies comparing 4 percent linoleic acid in rodents vs. 1 and 8 percent? And since arachidonic acid is what’s needed to produce those endocannabinoids in the first place, and the rodents in the studies are eating purified diets probably devoid of arachidonic acid, that might be a factor in human beings. I lean towards the rodents cannabinoid production being abnormally low on the 1 percent linoleic acid, rather than abnormally high on the 8 percent. Also, giving the animals omega 3’s on top of the 8 percent linoleic acid does protect from the fattening effect. But I wonder if it would be as effective against arachidonic acid? One study suggested krill as more protective than fish oil–because fish oil contained more arachidonic acid than krill.

        The authors of the 1 vs 8 percent linoleic acid studies are under the impression that linoleic acid intake is more like 8 percent. The study they cite was commented on with the suggestion that hydrogenation and waste went up as soy oil increased in the diet, putting the estimate for linoleic acid around the NHANES number. But then, I wonder how much linoleic acid livestock are eating now vs. 100 years ago, and how that affects their arachidonic acid levels.

        I don’t think it’s “the” cause. But it’s sort of hard to prove. You can start with people who’ve not been exposed to soy oil, try to make them fat. Or you could take somebody who’s been eating it all their life, and has 15 percent or more linoleic acid in their fat tissue. Epa and Dha might work. Going from the other side, a very low omega 6 fatty acid diet, though–if somebody has 50 pounds or more of body fat, and 15 percent is linoleic acid, feeding them 1 percent linoleic acid might not decrease linoleic acid metabolism all that much.

        One rationale they gave for doing these studies is that blockade of endocannabinoid signalling increased depression and suicide with Rimonabant. I am leery of weight loss through depression.

  • Eric – Golden, CO

    Nice post. Next up, mu opioids and kratom?

  • This Old Housewife

    Isn’t Marinol used in the treatment of cancer and chemotherapy? The VA has also been conducting studies on marijuana, Ecstacy, and LSD in the treatment of PSTD.

    Thank you for being the first of “our ilk” to break silence on marijuana. Free the Animal wrote about it, but from a user standpoint.

    • marinol is used for anorexia/cachexia in cancer; stimulates appetite & reduces nausea, “anti-emetic”

  • rs711

    little follow up ==> NIH presentation “Demystifying Medicine 2015 – Marijuana: then Highs and Lows” At 58min10sec point Dr.George Kunos explains why the in vitro &/or in vivo (mice) negative phenotype changes Bill talks about might be ‘reconciled’ by the fact that chronic heavy marijuana smoking rapidly desensitizes the CB1 receptors whilst endocannabinoids do not desensitize it (theory put forth by the brilliant Gerald Reaven. See tweet for full quote