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    When Science Goes To Pot Part III: Chatting With The Scientists
    By David Sloan | January 18th 2013 12:04 PM | 37 comments | Print | E-mail | Track Comments
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    David is a neuroscientist in the field of sensory-limbic circuitry. He published his debut novel, [Brackets], in October 2012. He is a member of...

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    In parts 1 and 2 of this series, I undertook a (much longer than anticipated) personal investigation into how scientists discuss the effects of cannabis as a way of trying to better it, both as a drug and as a cultural subject. The articles generated a great deal of discussion and many intriguing points were raised. Jimmy is a much smarter young man now.

    But even after all the reading, writing and discussion, I still had questions with unsatisfactory answers. So I decided to do the one thing that was even better than reading scientific articles: I talked to scientists.

    Two scientists were kind enough to grant me interviews: Dr. Deepak Cyril D'Souza, a psychiatrist and researcher at Yale University, and Dr. Steven Laviolette, a neuroscientist at the University of Toronto.  Both are experts on the neurobiology of cannabis, cannabinoids and the brain, and both were ideal and engaging interviewees who have my sincere thanks. I posed to them many of the questions that had come up in the discussions, and added a few new ones that came up while I was learning about their research. 

    Discussion with Dr. D'Souza

    Dr. D'Souza  conducted the 2005 study that I cited in part 1, in which different doses of THC were injected directly into the bloodstream. I asked him specifically about his report of elevated anxiety rates in his subjects, a finding which would seem to contradict the assumed affect of the main component of cannabis. "We need to be clear that cannabis and THC are not the same thing,…we did not fully appreciate this at the time that we conceived the study" he said, and noted (as commenters have also noted) that there are important differences in dosage and delivery between what he did in his study and what smokers receive. Furthermore, he pointed out that there are other chemicals which contribute to the net effect of smoking, including the presence of the anti-anxiety, anti-psychotic cannabidiol, which we have discussed elsewhere.

    I also asked him about the use of the words "psychosis" and "psychotic", and if what cannabis users experienced could be described as a temporary experience as a schizophrenic. He clarified, "Schizophrenia is a psychotic disorder. THC induces psychotic symptoms. I don't believe that any drug can model a complex disorder like schizophrenia. Elevated intravenous levels of THC can cause symptoms that resemble schizophrenia." He referenced this video of a journalist being injected with THC on BBC, for anyone interested.

    When I asked about his reports of paranoia and THC, and the commenter response that anyone would feel paranoid in the lab, he noted that in his double-blind study, people became paranoid only in the THC condition, not on the placebo condition. He also noted that, again, the effect was dose-dependent. He did concede that setting does matter a little in these studies.  He also cited the large anecdotal links between cannabis use and paranoia. For example in some surveys between 20% and 50% of individuals have reported paranoia, persecutory ideas, and hallucinations while under the influence of cannabis (see Here and Here).

    I also asked about specific findings that he had published. In one recent paper, (2012 Neuropsychopharmacology), he described that the symptoms of time overestimation and underproduction in his THC subjects was blunted in people who used 2-3 times a week. From what I've heard from users, the existence of tolerance does not come as a surprise. But he suggested that it was a surprising finding because 2-3 times per week was considered "light use," but that even that usage rate induced noticeable adaptive changes which weren't limited to the effects of how they experience time.  Behavioral effects, subjective effects, cognitive effects including effects on memory, hormonal responses and even EEG changes in response to THC were blunted in the 2-3 a week users. On the topic of EEGs, his lab also found that gamma and beta frequency EEG patterns were reduced in weekly cannabis users compared to non-users. What does that mean? It is a bit too early to tell-- he can only speculate.

    Discussion with Dr. Laviolette

    Dr. Laviolette is a specialist in the effects of the cannabinoid system on "emotional learning", which can mean a lot of things, but in his lab, it refers to reward-seeking behaviors and learning related to fear. He explained, “Cannabinoid transmission has a long and important involvement in our understanding of emotional learning because not only can modulation of cannabinoid receptors (either activation or blockade) regulate the formation and expression of emotional learning and memory, but the endocannabinoid system in general is a potent regulator of neuronal plasticity mechanisms related to learning and memory."

    I asked about the lasting effects of high doses of THC. He replied that his lab was focused on the acute effects, noting as an example that cannabinoid receptor activators in the amygdala can "increase the emotional salience of fear memories" and can affect activity in the prefrontal cortex remotely, but that this occurs at higher doses only.  His lab is undergoing further research into how higher doses of THC in young rats affects the actions of cannabinoids in adulthood, as a way of addressing "compelling evidence linking exposure to high levels of marijuana during adolescence to an increased risk of developing schizophrenia-related psychoses in young adulthood."

    In 2006, Dr. Laviolette published a review demonstrating the links between cannabinoid and dopaminergic systems. This relationship is of interest since dopaminergic systems are historically credited as the neurobiological root of addiction. And yet, addiction seems to be a low risk in cannabis users. "That's a very interesting and complex question," he responded.  He pointed out that the role of dopamine isn't restricted to a single "pleasure" signal, and even has a role in modulating aversive behaviors in the prefrontal cortex.  "I think we are beginning to realize that dopamine serves more as a general signal for any sort of emotionally 'salient' event, which acts to guide emotional learning and memory formation, be it reward or fear-related."  He noted that cannabinoids strongly influence dopaminergic signaling, but that the effects of their influence are still being studied by their lab and others.

    On How We Talk About Cannabis

    I asked Dr. D'Souza why it was that scientists and doctors (like himself) tended to describe the effects of cannabis and THC in negative terms. His answer was that his view of cannabis use was colored by his surroundings. As a physician in a hospital, he only sees the people with problems, but he is aware that there may be beneficial effects to cannabinoids.  In fact Dr. D’Souza’s lab is actively studying potential beneficial effects of cannabinoids including the effects of THC on pain, and on extinction learning.

    I asked both men if they thought that government agencies selectively emphasized negative research findings over positive ones. Dr. Laviolette said, "I think considering how far both the U.S. and Canadian Governments have evolved since the days of ‘Reefer Madness’ is generally quite encouraging. Indeed, the fact that it is actually possible to obtain marijuana for medical purposes is a massive leap forward considering the history of cultural hysteria that has surrounded marijuana in both the U.S. and Canada." But he also recognized that there was considerable trepidation by governments concerning marijuana. When I asked Dr. D'Souza specifically about the language of NIDA, he replied that he couldn't speak for the agency, but “I don’t get the sense that NIDA will only fund studies designed to show that marijuana is harmful.”

    I asked both men if they ever felt pressure to perform, publish or propose research that cast cannabis in a negative light. Dr. D'Souza was emphatic. "No. Absolutely not."  Dr. Laviolette added, "Personally no, I have not experienced any sorts of pressure one way or the other."

    On The Future

    One idea that was brought up during the article discussions was that cannabis has been around for so long that it's unlikely that we would learn anything new about it now. It turns out that there actually is a lot to learn. Dr. D'Souza pointed out that there were three historical phases of cannabis research. "There are the thousands of years of uncontrolled data. Then, beginning in 1963, [when THC was identified as the active ingredient] to the mid 1970’s, there was an increase in research including controlled studies. Then not much happened for about 15 years because the mechanism of action of THC remained an enigma.  Then in 1988, the cannabinoid receptor was discovered." From that point, studies on cannabinoids have increased exponentially.

    Dr. Laviolette explained that "the formal identification of the brain's endocannabinoid system is relatively recent. However, the progress over the last few years has been remarkable," citing as an example the increased understanding of not just Cannabinoid Receptor 1 in the brain, but also Cannabinoid Receptor 2.  He noted that there is still a great deal of work to be done to discover the anatomical and functional roles of the endocannabinoid system, specifically as they relate to how they modulate synaptic plasticity, and how that modulation translates into changes in behaviors.

    Both researchers are excited by the prospects of useful medical knowledge and applications coming out of cannabinoid research.  In fact, both of them referenced the potential therapeutic applications of cannabidiol. But they also strongly suggested that there is much more research to be done on cannabis and cannabinoids.

    Dr. D'Souza expressed concern because, although he believes that the majority of people who use cannabis may not experience negative effects, the connection between cannabis use and an increased risk of schizophrenia is still being debated. "If there is a link between [cannabis] and schizophrenia, which is a terrible disorder to have, then we should modify the risk factors."  He didn't know precisely what determines a higher risk, but that "some are more vulnerable than others." "The potential consequences of a lifelong disorder shouldn't be minimized." He added that the move to legalize cannabis suggests that more people will be using it. And that means "the studies need to continue.”

    Taking a step aside, I wanted to make one (absolutely final) comment. An idea that was brought up in the commentary on the articles was that the only relevant debate about cannabis is its legalization, and that any studies on cannabis now are inconsequential to the sociopolitical discussion. Your opinions on this point are your own. But I've learned from this experience that the scientific debates in the study of cannabis, in neuroscience, in immunology, in pharmacology, and in other fields are not done. Not even close. That may not matter to users, or voters, but it should matter somewhere, and not just to the academics.

    Dr. Laviolette offered this fitting conclusion: "Those of us in the basic neuroscience community go where our data takes us, both from the clinical and basic research sides of the equations. I think there are extreme positions on both sides of the debate and the best thing to do is to wait on the science. Reliable, solid, peer-reviewed data is the best way to inform public health policy."

     

    Comments

    "When I asked Dr. D'Souza specifically about the language of NIDA, he replied that he couldn't speak for the agency, but 'I don’t get the sense that NIDA will only fund studies designed to show that marijuana is harmful.'"

    This is not true as reported here:

    http://www.thedailybeast.com/newsweek/2010/11/03/why-it-s-hard-to-do-mar...

    “NIDA…has a congressional mandate to only study substances of abuse as substances of abuse,” says Don Abrams, chief of hematology/oncology at San Francisco General Hospital and professor of clinical medicine at the University of California, San Francisco, who has done studies on marijuana in the past. In his experience, studies that aren’t targeted at the dangers of marijuana or ways to treat marijuana abuse and addiction rarely pique the interest of NIDA, which is also the only legal marijuana source for research in America.

    And here:

    http://www.maps.org/research/mmj/

    "[The Multidisciplinary Association of Psychedelic Studies's] efforts to initiate medical marijuana research have been hindered by the National Institute on Drug Abuse (NIDA) and the Drug Enforcement Administration (DEA) since our founding in 1986. NIDA's monopoly on the supply of marijuana for research and the DEA's refusal to allow researchers to grow their own has paralyzed medical marijuana research, and for over ten years MAPS has been involved in legal struggles against the DEA to end this situation."

    "I asked both men if they thought that government agencies selectively emphasized negative research findings over positive ones. Dr. Laviolette said, "I think considering how far both the U.S. and Canadian Governments have evolved since the days of ‘Reefer Madness’ is generally quite encouraging."

    Doctor or no doctor, he must be joking. Both the US and Canadian governments are as resistant as ever to legalization. The current situation in Canada is that the government is taking away the right for MMJ folk to grow their own cannabis. The Obama Administration still holds cannabis in Schedule 1 and maintains that it has no medicinal use.

    Nope. Reefer madness is still very much alive and well and living in North America (and most other places, too.)

    It's a case of de-evolution in fact. In 1972 Nixon's hand-picked conservative cronies were able to produce an honest, thoughtful document on the subject. Nixon was furious of course, and their careers suffered; the lesson was learned. Today we have people who repeat simple-minded talking points like "Cannabis is an illegal drug. Illegal drugs are bad. Therefore cannabis is bad." Someday we will have to answer for this madness. How will we explain it?

    Hank
    Wait, so (1) hand-picked cronies somehow (2) produced an honest document?

    Which of those terms do you not understand? Either Nixon was not as bad as you claim or conservatives are not as bad as you claim.  The 'the evidence was so obvious even X had to agree' argument stopped working when you were in 8th grade.

    Nixon was the most progressive Republican since Teddy Roosevelt, he signed wage control bills, escalated a war started by Kennedy and created every environmental law we have - yet people who never met him insist they know him so well they can tell us how 'furious' he was over something because they think he was conservative. He was not a conservative, he was not even close to conservative. He was instead a social authoritarian determined to control how people behave, just like we have in office right now.
    Isn't the fact that he tossed their recommendations and stepped up the anti-cannabis agenda instead evidence enough for you? He clearly expected them to rubber stamp his new drug war. However I will see if I can find actual citation.

    Are you denying that Nixon hated hippies??

    "He was instead a social authoritarian determined to control how people behave"

    This explains perfectly why he saw cannabis as a threat.

    This is not the first time people tasked with the job took a close look at the "marijuana menace" and found that it didn't exist. Same thing happened right after all the reefer madness hype when LaGuardia's NYC commission looked at the problem.

    Scratch the word conservative if you think I used it carelessly- it doesn't affect my argument.

    Gerhard Adam
    But I've learned from this experience that the scientific debates in the study of cannabis, in neuroscience, in immunology, in pharmacology, and in other fields are not done. Not even close.
    Funny how cannabis [with its wide popular support] has taken decades of review, study, and legal issues because of its "suspect" nature.  Yet, if someone wishes to see the thoroughness of the studies that examine effects of long-term exposure to GM foods, then suddenly the science is settled, or it's simply "unethical" to do this on humans [despite it's presence in the food supply].

    I realize that this isn't about GM foods, but I wouldn't be a bit surprised to acquire the "anti-science" label just for bringing up the topic again.  Perhaps you could address this disconnect?
    Mundus vult decipi
    Renaisauce
    This is a very good point, and worthy of a whole other discussion on "when is enough science really enough?" In the case of GM foods, things are constantly changing (new crops, new genes, new lands, changes in environment and insects and whatever), so it should never not be studied.

    Cannabis is in an interesting scientific niche because so much about how it works, and what it should and should not be used for, was only revealed as our overall understanding of neuroscience and other fields, along with newer and better tools, came decades after it had established its cultural integration and subjective reputations, with everything that went with them. In addition, like with GM crops, the field is in flux.  The manipulation of different concentrations of THC/cannabidiol in different versions of the drug (which will likely continue to change), the increase of use in different populations, the application of "natural" and "synthetic" THC experimentally for different medical treatments, its co-use with other drugs,  the effects of the other 68+ cannabinoids in cannabis, etc. offer a seemingly inexhaustible set of things to study. And science moves one fact at a time, and policy has not that patience. 


    So when is enough enough? I don't know. I'll have to think about it more.
    How is learning more about the physiological mechanisms going to change anything as far as public policy, except maybe in some instances in how the drug is used medically? What exactly do you mean by public policy? If you mean ending prohibition, I can't imagine what you are expecting to learn that will change anything. We already know in great detail how this drug affects individuals and society as a whole. The question has been looked at closely by commissions of experts over and over who have determined that prohibition is not justified. Learning more about neuroreceptors is going to change that how?

    By the way, only since our last discussion, the data used in the latest big scare story about pot (that it lowers IQ in heavy, dependent users who start using at a young age), was re-analyzed by another group who did not find this result. They think it is probably socioeconomic factors causing the effect. And so it goes...

    John Hasenkam
    and that any studies on cannabis now are inconsequential to the sociopolitical discussion.

    Reminds me of something I read in a Dr. Atkins book: that in 1949 Oxford Uni was approached to do a big study on nutrition and they rejected that because there was already enough known about nutrition. 


    As to the sociopolitical issues, which is really a moral issue, if the risks of cannabis were that severe and given it is the most widely used recreational drug then surely by now we should have much more substantial evidence of harm? We will be far better off now that the bods are focusing on the therapeutic potential of cannabidiol which range from management of atherosclerosis to Multiple Sclerosis to autoimmunity to inflammation to some cancers(mainly brain tumours, amongst the most untreatable). Both THC and cannabidiol are potent antioxidants to boot! Regular marijuana use has a net negative effect on health but I suspect only at the margins. That habit will impede the anti-viral response, though perhaps not the anti-bacterial response. The biggest health problem though could be that regular smoking can slam you into the couch making you unproductive leading to a loss of income and I suspect being in a low socioeconomic group carries the a bigger health risk. 




    BTW David, the anxiety-pot linkage is very real but only seems to apply to a small subset of people. I've known people who have had acute anxiety episodes of sufficient intensity to stop them smoking. I suspect that some of these anxiety attacks are misdiagnosed as acute psychotic episodes. People with anxiety conditions need to think very carefully about marijuana. Sadly though if recent research is accurate they should also avoid alcohol. That's a shame because as Seigel argues in Intoxication, the liking for psychoactive drugs, certainly not confined to humans(his book has some wonderful stories of animals on drugs), is essentially a biological drive. So if anyone is pathological it is the abstainers. :)  
    Just to clarify, if you reread my earlier comments, I never said there was nothing left to learn about cannabis. I said the new stuff we are learning is all about the mechanisms, which your interviewees only confirmed. That is all well and good. What is NOT new information is the harms. No new harms have been uncovered. Even concern about possible links with psychosis and schizophrenia is an old concern, as my citations showed. And still we don't have the answers there.

    John Hasenkam
    These types of results are promising and deserve more attention. A Molecular Link Between the Active Component of Marijuana and
    Alzheimer's Disease Pathology

    Mol Pharm. 2006 ; 3(6): 773–777. doi:10.1021/mp060066m



    It is noteworthy that THC is a considerably more effective inhibitor of AChE-induced AƒÀ deposition than the approved drugs for Alzheimer's disease treatment, donepezil and tacrine, which reduced AƒÀ aggregation by only 22% and 7%, respectively, at twice the concentration used in our studies.7 Therefore, AChE inhibitors such as THC and its analogues may provide an improved therapeutic for Alzheimer's disease, augmenting acetylcholine levels by preventing neurotransmitter degradation and reducing AƒÀ aggregation, thereby simultaneously treating both the symptoms and progression of Alzheimer's disease
    Renaisauce
    Ooh, that is very interesting. I'll have to read that study. Thank you for bringing it to my attention. I must be behind on my Alzheimer's research because I didn't know acetylcholine had been implicated in the pathology (I assume AfA refers to A-beta? OR maybe not.)
    John Hasenkam
    Yep, A-beta, there are a number of studies that point to THC and CBD being protective against A-beta and its associated toxicity. I also wonder if the ACHe linkage may relate to the anxiety problems that can occur with THC(tentative, some early antidepressants are anti-cholinergic and mirtazapine, a new one, is very much anti-cholinergic). 

    Ach decline is common in Alz, apparently cholinergic neurons are particularly susceptible to A-beta toxicity. As Ach also plays an important role in modulating inflammation the loss of central Ach may pave the way for sustained inflammation. Additionally Ach is important in regulating cerebral microcirculation, as is nore which can also decline in Alz, and circulation issues have long been associated with Alz. There are individuals who have high A-beta loads and do just fine which causes me to speculate that in these individuals the cholinergic neurons may be protected in some way from A-beta toxicity; especially given Ach is very important for memory consolidation. That is, the loss of Ach precipitates many of the bad aspects of A-beta and preserving Ach may be a cardinal strategy to pursue. Ach is produced predominantly, I think, in the brain stem(nucleus of Maynert). Stem cells anyone?
    vongehr
    any studies on cannabis now are inconsequential to the sociopolitical discussion. ... the study of cannabis, in neuroscience, in immunology, in pharmacology, and in other fields are not done.
    So you stay with this naive scientistic politically biased dogma that sociopolitically consequential pot-science is mainly neuro-medical-poison-addiction-reefermadness, and then you are all surprised that people don't care about such "science" as it is obviously biased from the start?
    There is no funding for scientific studies about how to best use pot to advance academic education, as a means for freeing stuck association patterns, as entactogen increasing the ability to understand opposing views, ...

    Conclusion of your series: There is no trustworthy science that can be found on this subject, thus, who has not personally tried pot should not be listened to.  Come back after having used several times in different circumstances AND having read up on drug-war issues.  Otherwise, stop talking about "sociopolitical discussion".  Leave those to people who are not afraid of the monsters they bottle up inside and fear to face or unleash if they get high.
    Renaisauce
    Woah, Sascha.  
    I've really struggled writing a good response to this comment, because I think my overall view of what is trustworthy, useful, subjective, objective and biased (at least on this topic) are very different than yours, and our reactions to what I read and wrote are very, very far apart. And that's fine, it happens. 

    But I found the strength of your response intriguing, and it took me all morning to figure out some of the reasons why. 

    A few points: 

    (1) You suggested that only people who have used cannabis multiple times under different settings can have any opinion on it whatsoever. I fundamentally disagree.

    (2) You suggested that I know very little about the drug war. You may actually be more knowledgeable about some aspects of the war, but I'll bet that, of the two of us, I'm the only one that has actually lived and worked in Colombia AND Northern Mexico. I could be wrong.

    (3) You suggested that my reason for not trying pot is that I'm afraid that my fears will be unleashed and turn into monsters that I must face if I get high. Why would I think that would happen? Exactly what part of the description of getting high would make me arrive at that conclusion? I found that there was a small risk of panic attacks and increased anxiety, but I don't think of it as that fear cabinet thingy from Harry Potter 3. Maybe that happens with LSD.

    (4) You suggest that all academic science that even suggests something negative about cannabis is biased. I think that's unfair, and I think any perception of bias that you might ascribe to those studies would also apply to peer-reviewed findings that suggest positive things about cannabis. and if that's true, neither side should ever look to science to support their opinions. Was that what you were saying?

    (5) You suggest that cannabis should be part of our educational system as a tool to show kids how to think outside the box. Somebody's been reading about Steve Jobs. Interesting. Out of curiosity (and this is a serious question), are there companies in Europe that have shown that they are more productively inventive because their engineers and researchers are getting high on or off the job? Artist colonies don't count.













    I don't think of it as that fear cabinet thingy from Harry Potter 3. Maybe that happens with LSD.
    Don't underestimate pot.
     
    Even so, there is more to "unleashing your fears" than facing a boggart. Perhaps Sascha was hinting at something worse than a panic attack? A very mild experience that undermines your concept of reality or challenges your place in society is more of a threat than a frightening hallucination.
     
    MikeCrow
    Or getting a criminal record for an intoxicant that's far milder than the legal intoxicant.
    Never is a long time.
    vongehr
    I found the strength of your response intriguing, and it took me all morning to figure out some of the reasons why.
    The strength of my words comes from the strength of my thoughts.
    You suggested that only people who have used cannabis multiple times under different settings can have any opinion on it whatsoever. I fundamentally disagree.
    Set and setting - everybody who knows just a little about drugs knows this ... and please do not forget that I wrote this under the given background of there being no trustworthy information out there.  If such were available, we would not have this discussion.
    You may actually be more knowledgeable about some aspects of the war, but I'll bet that, of the two of us, I'm the only one that has actually lived and worked in Colombia AND Northern Mexico.
    David - I will not descend to counting black friends.  Such a move from you either reflects your style, or the suggestion of that I reside or even respond on that kind of level is meant as an insult perhaps.
    You suggested that my reason for not trying pot is that I'm afraid that my fears will be unleashed and turn into monsters that I must face if I get high. ...
    I did neither imply this as your personal problem necessarily nor did I imply the monsters to be the LSD reefer madness stuff.  The monster you may see is for example you as I see you now. Sartre would call it The Look. (No - I don't like Sartre.)
    You suggest that all academic science that even suggests something negative about cannabis is biased.
    No, I certainly did not. You would have to do quite some ad hoc interpreting in order to force this interpretation.
    You suggest that cannabis should be part of our educational system as a tool to show kids how to think outside the box.
    No, I did not! The frontal cortex is not even fully wired up before age 25. You automatically, unconsciously like a little cog-wheel, construct narratives about all people who talk reasonably about drugs ultimately selling AIDS-infected needles on school grounds. What I actually talk about (and have written about) is partially called "cognitive enhancement" and usually involves more adderall and green tea than pot.
    (and this is a serious question), are there companies in Europe that have shown that they are more productively inventive because their engineers and researchers are getting high on or off the job?
    Yes, sure, European companies put pictures of stoned engineers onto packaging in order to get more government contracts, which is why in Germany engineers customarily offer joints during job interviews. Again David - if you want to talk and be taken seriously by people who are as serious as me, perhaps you need to start being serious?!?  For some here on Science2.0, simply supporting the established version is professional and thus serious, but again, it is either stupidity or semi-conscious pretense and deception if you then behave all surprised about that people mistrust all information that is given to them by any sort of source that draws from authority under corrupted labels like "science".
    John Hasenkam
    There is no funding for scientific studies about how to best use pot to advance academic education, as a means for freeing stuck association patterns, as entactogen increasing the ability to understand opposing views, ...
    Very interesting point. While a recent study claimed pot very much lowered iq(now debunked) there are older studies indicating regular pot smoking can increase intelligence(CMAJ 2002 I think). There are studies suggesting marijuana can enhance creativity. I don't want to go neurological on this, that's just arm waving and pointless. Pot can definitely help you get some "emotional distance" from an issue, allowing you to recast the problem. Many psychoactive drugs seem to provide this benefit but I suspect it is in those individuals who have long labored on problems and are seeking some means to induce a cognitive shift. 



    There are a large number of good studies pointing to significant neuroprotection potential for cannabinoids and some striking indications that cannabidiol in particular could have many benefits in relation to immunologic conditions; especially the ever present one, inflammation. There is even a Nature Medicine study claiming that oral administration of THC markedly reduced atherosclerosis in the rabbit variant that gets that condition very frequently. The studies on psychosis, purported cognitive decline, even lung damage, are conflicting. There is a psychosis risk for heavy smokers under 21-25 but the failure to find increased rates of schizophrenia in populations with heavy marijuana use suggests marijuana is precipitating a latent propensity. The lung damage is probably the biggest issue but that is easily solved with vaporisers. Cannabinoids demonstrate considerable promise in relation to neuropathic pain. That could be very important in the near future because the USA has a big problem with prescription opioid related deaths and events. Only yesterday the Aus govt declared a review on the prescribing of opioid based pain killers because the prescribing rates have gone through the roof in recent years. What an absurdity, all those highlly addictive drugs available on prescription while the relatively non-addictive alternative is demonised as the devil's weed. 

    What is so sad about pollies sticking their grubby noses in all this is that there are now studies coming out showing how MDMA can be useful for PTSD, LSD for alcoholism(done in the 60's and recently), that a middle age onwards dopamine boost is not such a bad idea(Erdos!), and even the suggestion that the analogs of THC(HU211?) with approx x100 the affinity for the CB 1 receptor, increase neurogenesis which is somewhat ironic because the legal drug, alcohol, has been demonstrated to impede neurogenesis(animal model, circa 40% reduction); the last thing you want in an aging brain. Politics and stupid Leary put back research on this by 50 years if not longer. That has to change because the future is clear: cognitive enhancement will be sought by a great many. 


    I suspect a major fear of drug use is the idea that you will "lose control". Yeah well if that happens you probably had some daemons lurking above the neck and should have dealt with that long ago. "Losing control" is the whole friggin' point! 
    vongehr
    about "now debunked", I asked recently on my corkboard
    "Now a paper that claims pot does not make stupid: Proceedings of the National Academy of Sciences (PNAS), doi: 10.1073/pnas.1215678110. Let us see whether FOX and "Real Clear Science" are as happy about promoting this one as they have the reefer madness lately."
    Well, and of course Science2.0 was implied (is BFF with RCS) - have a look and try finding the debunking here.  We like to bunk, not debunk.  Who cares about innocent people in prison if you can write polemics and get to go on FOX for all your buddies to see how important you are.
    Yes, exactly; we are going to hear that "pot lowers IQ" for a long time.

    The real insanity is the delusion of NIDA scientists who think they are going to at long last "discover" some harm that will then justify the decades-long slide into a police state.

    MikeCrow
    Oh, Oh, Oh, "Pot lowers IQ, CO2 going to melt the planet, News at 11:00"

    bwhahahahahaha
    Never is a long time.
    MikeCrow
    John Stossel routinely advocates legalization of all drugs, on FOX, where he has his own show. So while there are a number there who have a staunchly anti-drug position, not everyone does, nor does there appear to be a mandate where that view has to be maintained to be on the air.

    just saying........
    Never is a long time.
    Hank
    Right, that isn't a conservative position but Isabel conflates Republican with conservative, which is the first mistake, and then Nixon with conservative, an even bigger mistake.  Nixon has as little in common with conservative Republicans as Obama has with Kennedy.
    Oh dear. I did no conflating, I meant "social conservative" I guess. Or whatever. I know well that legalization of pot is not a liberal issue. I argue this point all the time on Drugmonkey blog. My whole point was that "ex-stoner" Obama's administration is LESS truthful about drugs than Nixon's associates were, rather than more progressive, rather than "evolved" as was suggested in the OP.

    Someone used "conservative" incorrectly oh my gosh the whole thread must be derailed.

    Hank
    Someone used "conservative" incorrectly oh my gosh the whole thread must be derailed.
    Welcome to the Internet!
    Yeah well if that happens you probably had some daemons lurking above the neck and should have dealt with that long ago. "Losing control" is the whole friggin' point!
    Very sixties. Let's pretend acid is all nice and cozy and blame the victim if things turn nasty.

    Who dares claim they have exorcised their own demons? Take some acid and talk to me - I bet I can freak you out! :)
     

    MikeCrow
    I'm sure you could, that picture of you in that spelunking hat is enough to scare the children on Halloween ;)

    I see it as an amplifier of emotions, good, or bad. If you cannot get a grip on the negative emotions that might come up, it will freak you out. But with positive emotions it can be quite enjoyable.
    Never is a long time.
    UvaE
    If you cannot get a grip on the negative emotions that might come up, it will freak you out. But with positive emotions it can be quite enjoyable.
    Let "it" = life, love, children or work, and your statement remains true. 

    MikeCrow
    Well said!
    Never is a long time.
    John Hasenkam
    Very sixties. Let's pretend acid is all nice and cozy and blame the victim if things turn nasty.
    Who dares claim they have exorcised their own demons? Take some acid and talk to me - I bet I can freak you out! :)
    Good luck with that challenge Derek. You are making the error of thinking the effects are the same for everybody. The last time I took a trip I had sore ribs for a week from laughing so much. I have walked city streets, talked to coppers, sat in crowded theaters while so high sweat was pouring off me. I have attended management board meetings stoned off my tree and still made more sense than many at the meeting. It is very hard to freak me out because I went through horrors in childhood that make anything people throw at me seem mundane in comparison. Your approach seems rather Freudian\Jungian, as if everyone is carrying within them some deep horror that must be constantly repressed. I don't have a Heart of Darkness and I suspect the greater majority don't. Joseph Conrad may have embraced original sin and the corruption of all creation as real things, I don't.  



    The whole point of psychology\psychiatry is about "exorcising demons", as is much of religion. Buddhism is precisely about uncovering those less than pleasant aspects of our being. So by your logic all that is terribly dangerous too. It is, it is known in some Buddhist practices mental breakdown is a real risk. It is known that a certain percentage of people using illicit drugs are self- medicating. It is known that psychiatric drugs, particularly antipsychotics, have dangerous side effect profiles far in excess of marijuana. 


    The very reason I made reference to "stupid [Timothy] Leary" was because the bloody hippies through their reckless endorsement and astounding ignorance turned drug use into a free for all. In these days though there are sites like Erowid, you can bone up on how to use the drugs, you can obtain a perspective that doesn't make grand generalisations about how no-one should ever use these drugs. If the results from Portugal are anything to trust it would seem that their approach, an approach that allows drug users to become more informed, to seek help without fear of legal prosecution, is resulting is less drug crime, less drug use, and a greater awareness of the dangers of illicit drug use. 


    Since you are so worried about the demons I suggest you also tell everyone to stop drinking alcohol because in Britain and Australia alcohol associated violence is a big problem. Alcohol is just as capable of releasing the demons and it releases the savage ones. A few years ago some bod in Britain was dragged over coals because he suggested that one way to address alcohol related violence was for the police to hand out joints. It's not just a bad idea but getting stoned after you are drunk is a recipe for disaster, it often floors people. I imagine the bod knew that because it that will surely stop violent behavior. :) 




    vongehr
    I have attended management board meetings stoned off my tree and still made more sense than many at the meeting.
    Yes, of course. "still"?

    Good luck with that challenge Derek...
    etc.
    Everyone knows you are not really going to trip with me to see if I can freak you out, so there is no point in making big speeches about it.
    So by your logic all that is terribly dangerous too...
    etc.
    Since you are so worried about the demons...
    etc.
    Oh come now, that is a complete strawman and ad hominem at that. You can do better :)
     



    John Hasenkam
    Sorry Derek I thought you were implying that anyone on acid can be freaked out. I've heard that claim often enough. There is\ was a trend in psychology and psychiatry to the effect that everyone has some hidden demons lurking in them that must be outed. I'm not sure that trend has completely died and the DSM 5 seems to be going further down that road. 
    Dubious Virtue
    "Reliable, solid, peer-reviewed data is the best way to inform public health policy."
    Should that be epidemiological data or data from a very narrow perspective?
    What happens when the two are contradictory?
    John Hasenkam
    Another bout of insomnia so I spent the early morning hours downloading various articles on pot and and its consequences. Haven't read them yet but the cliff notes version goes like this:
    There is clear and very worrying evidence that heavy cannabis use beginning in the mid teenage years not only predisposes towards psychosis but also causes structural alterations, particularly reductions in hippocampal volume(12%). I place two caveats over the structural changes: 1. no such thing as a "normal brain", human brains are remarkably variable in their morphology, and 2. Imaging studies are not pictures, tend to be contradictory, and can be very difficult to interpret. 

    If these structural changes are about neurotoxicity then it is puzzling that the effect only seems apparent in those early developmental years, when one would expect a stronger protective effect from any toxicity. Additionally there are host of studies demonstrating cannabinoids, especially those that bind the CB2, as do THC and CBD, can have potent neuroprotective properties. 

    Cannabinoids do demonstrate some remarkable anti-inflammatory properties, which seems at odds with the neurotoxicity argument. Now it could be the case, as paradoxical as it sounds, that too much reduction in so called inflammatory mediators is not good for the developing brain. For example, TNF can have neuroprotective properties and perhaps, only that, il-1 plays a role in sustaining LTP. So the reduction in hippocampal volume may not be neurotoxicity per se but rather the reduction in LTP is limiting hippocampal volume. Guess! Keep in mind that hippocampal volume can vary markedly in a very short time(London cabbie study).

    The other confounder here is a CMAJ prospective study which found pot increased IQ in light smokers, decreased it slightly in heavy smokers, who upon cessation recovered. This was a study of teenagers. The problem here is other studies showing that cannabis use, like other drugs, seems to occur more often in the more intelligent. 

    CB 2 agonists do appear to promote neurogenesis and neurotrophic factors. 
    -------
    All very confusing. It has been years since I read literature on this subject but this discussion prompted me to do an update so I've downloaded a number of recent articles. 

    As a public health issue, the emergence of strains with a much higher THC\CBD ratio is worrying, especially given cannabinoids are lipid soluble so can build up in the system. For heavy users it can take full month to wash out 90% of the cannabinoids. Given the increases in teenage pot use and the strong association with cognitive problems that is a concern. 

    If people want to smoke their pot on weekends so they can really listen to music, and by golly it is great for enhancing music appreciation, it aint gonna harm you. If people smoke every day it will reduce your productivity and I suspect will impede cognition not because of neurotoxicity but because it robs you of drive. However, all things considered, even after heavy long term use, cessation seems to reverse the negative effects. 

    As best as I can tell this Wiki entry seems to do a good job on summarising some recent findings. 

     



    MikeCrow
    If people smoke every day it will reduce your productivity and I suspect will impede cognition not because of neurotoxicity but because it robs you of drive.
    I suppose it can, but it doesn't have to.
    Never is a long time.