Thursday, January 31, 2013

Legalize Marijuana at the Federal level. | We the People: Your Voice in Our Government

Legalize Marijuana at the Federal level. | We the People: Your Voice in Our Government



 Legalize Marijuana at Federal level. | #WeThePeople: ur Voice n Our Government
Total signatures on petition 23977

Cannabis Patient Network - YouTube

Cannabis Patient Network - YouTube

Autism and Cannabis | Marijuana Therapy

Autism and Cannabis | Marijuana Therapy

Suppression of pendular nystagmus by smoking cannabis in a patient with multiple sclerosis

Suppression of pendular nystagmus by smoking cannabis in a patient with multiple sclerosis

The GREAT CANNABIS REBELLION -Newspaper4 #Health+ #HumanRights

Health - The GREAT CANNABIS REBELLION

The GREAT CANNABIS REBELLION - Newspaper4 #HealthChoice a #HumanRights

Health - The GREAT CANNABIS REBELLION

Cannabis and Creativity | Psychology Today

Cannabis and Creativity | Psychology Today


clip from article:

Cannabis and Creativity

Should drugs be used to facilitate creativity?
Cannabis is reportedly the most popular illicit substance in the world.  Its estimated one-time use in 2009 ranged from125 million to 203 million people (aged 15-64) (UNODC, 2011).  According to a report by WHO, cannabis use has increased since the 1960s in North America, Europe, and Australia particularly among young people and is commonly associated with youth culture.  The report also summarizes the acute and chronic effects of cannabis use including various cognitive (learning and recalling information, integrating complex information, increased risk of psychotic disorders) and psychomotor impairments (higher risk of accidents when driving intoxicated).
In light of these effects, it was interesting to find a study on the effects of smoking cannabis on creativity.  Schafer and colleagues (2011) reviewed literature suggesting that the effects of cannabis on creativity have not been extensively studied nor are the mechanisms by which it stimulates creativity well understood.  However, they suggested that cannabis produces psychotomimetic symptoms, which in turn might lead to connecting seemingly unrelated concepts, an aspect of divergent thinking considered primary to creative thinking.  A drug induced altered state of mind may indeed lead to breaking free from ordinary thinking and associations, thereby, increasing the likelihood of generating novel ideas or associations.  Weiner (2000), for example, noted “From American Indian use of peyote to Chinese people using plum wine, to Coleridge’s opium use, and Hemingway’s alcohol consumption, individuals have found that the exaggerated emotions and altered perspectives they’ve gained from drugs stimulated their creativity” (p. 211).
Schafer et al. identified two groups of participants, one high (average age 21.37) and the other low (average age = 21.62) on trait creativity and tested them in two counterbalanced conditions: non-intoxicated (day 1) and intoxicated (day 7).   Creativity was measured using three tasks: (a) verbal fluency (give as many responses linked to a given alphabet in 60 seconds); (b) category fluency (give as many verbal responses linked to a given concept category in 60 seconds); and (c) Mednick’s Remote Associates Test (give one word that links three given words; 4 minutes given for each of the 16 word triads on the test).  They found that while both trait creative groups scored higher on state schizotypy as assessed by a self-report questionnaire on the intoxicated day, there were no significant differences between the two groups on the Remote Associates Test, thus ruling out the possibility that increased schizotypy played any role.  However, verbal fluency scores for the low trait creativity group increased to the level of the high trait creative group on the intoxicated day, but the latter group’s scores did not differ on the two days.  Also, the category fluency scores did not differ on the two days, but the high trait group performed better than the low trait group on both days.[read more at link}
References
Cummings, N. A. (2012). How it was and how it was disrupted. In Cummings, N. A. & O’Donohue (Eds.).  Restoring Psychotherapy as the first line intervention in behavioral care (pp.36-62). NY: Ithaca Press.
Kennedy, R. (2012, April 4). How that sausage of happiness is made. The New York Times, The Arts, pp. c1, c5.
Schafer, G., Feilding, A., Morgan, C.J. A., Agathangelou, M., Freeman, T., & Curran, H. V. (2012).  Investigating the interaction between schizotypy, divergent thinking and cannabis use.  Consciousness and Cognition, 21, 292-298. doi10.1016/j.concog.2011.11.009
Weiner, R. P. (2000). Creativity & beyond: Culture, values, and change.  Albany, NY: State University of New York (SUNY) Press.
[read more at link]

Cannabis-induced cytotoxicity in leukemic cell lines: the role of the cannabinoid receptors and the MAPK pathway

Cannabis-induced cytotoxicity in leukemic cell lines: the role of the cannabinoid receptors and the MAPK pathway

Cannabis-induced cytotoxicity in leukemic cell lines: the role of the cannabinoid receptors and the MAPK pathway

  1. Wai Man Liu
+ Author Affiliations
  1. From the New Drug Study Group, St Bartholomew's Hospital (SBH), London, United Kingdom; the Department of Medical Oncology, SBH, London, United Kingdom; the Centre for Cancer Therapeutics, Institute of Cancer Research, Surrey, United Kingdom; the Department of Medical Oncology, Charterhouse Square, London, United Kingdom; and the Barry Reed Oncology Laboratory, SBH, London, United Kingdom.

Abstract

Δ9-Tetrahydrocannabinol (THC) is the active metabolite of cannabis. THC causes cell death in vitro through the activation of complex signal transduction pathways. However, the role that the cannabinoid 1 and 2 receptors (CB1-R and CB2-R) play in this process is less clear. We therefore investigated the role of the CB-Rs in mediating apoptosis in 3 leukemic cell lines and performed microarray and immunoblot analyses to establish further the mechanism of cell death. We developed a novel flow cytometric technique of measuring the expression of functional receptors and used combinations of selective CB1-R and CB2-R antagonists and agonists to determine their individual roles in this process. We have shown that THC is a potent inducer of apoptosis, even at 1 × IC50 (inhibitory concentration 50%) concentrations and as early as 6 hours after exposure to the drug. These effects were seen in leukemic cell lines (CEM, HEL-92, and HL60) as well as in peripheral blood mononuclear cells. Additionally, THC did not appear to act synergistically with cytotoxic agents such as cisplatin. One of the most intriguing findings was that THC-induced cell death was preceded by significant changes in the expression of genes involved in the mitogen-activated protein kinase (MAPK) signal transduction pathways. Both apoptosis and gene expression changes were altered independent of p53 and the CB-Rs.
  • Submitted March 29, 2004.
  • Accepted September 10, 2004.

JCI - Inhibition of skin tumor growth and angiogenesis in vivo by activation of cannabinoid receptors

JCI - Inhibition of skin tumor growth and angiogenesis in vivo by activation of cannabinoid receptors

Nonmelanoma skin cancer is one of the most common malignancies in humans. Different therapeutic strategies for the treatment of these tumors are currently being investigated. Given the growth-inhibiting effects of cannabinoids on gliomas and the wide tissue distribution of the two subtypes of cannabinoid receptors (CB1 and CB2), we studied the potential utility of these compounds in anti–skin tumor therapy. Here we show that the CB1 and the CB2 receptor are expressed in normal skin and skin tumors of mice and humans. In cell culture experiments pharmacological activation of cannabinoid receptors induced the apoptotic death of tumorigenic epidermal cells, whereas the viability of nontransformed epidermal cells remained unaffected. Local administration of the mixed CB1/CB2 agonist WIN-55,212-2 or the selective CB2 agonist JWH-133 induced a considerable growth inhibition of malignant tumors generated by inoculation of epidermal tumor cells into nude mice. Cannabinoid-treated tumors showed an increased number of apoptotic cells. This was accompanied by impairment of tumor vascularization, as determined by altered blood vessel morphology and decreased expression of proangiogenic factors (VEGF, placental growth factor, and angiopoietin 2). Abrogation of EGF-R function was also observed in cannabinoid-treated tumors. These results support a new therapeutic approach for the treatment of skin tumors. [ read more at link]

History of Cannabis and Its Preparations in Saga, Science, and Sobriquet - Russo - 2007 - Chemistry & Biodiversity - Wiley Online Library

History of Cannabis and Its Preparations in Saga, Science, and Sobriquet - Russo - 2007 - Chemistry & Biodiversity - Wiley Online Library

Keywords:

  • Cannabis;
  • Cannabinoids;
  • Marijuana;
  • Medical history;
  • Ethnobotany;
  • Genetics;
  • Tetrahydrocannabinol (THC);
  • Cannabidiol

Abstract

Cannabis sativa L. is possibly one of the oldest plants cultivated by man, but has remained a source of controversy throughout its history. Whether pariah or panacea, this most versatile botanical has provided a mirror to medicine and has pointed the way in the last two decades toward a host of medical challenges from analgesia to weight loss through the discovery of its myriad biochemical attributes and the endocannabinoid system wherein many of its components operate.
This study surveys the history of cannabis, its genetics and preparations. A review of cannabis usage in Ancient Egypt will serve as an archetype, while examining first mentions from various Old World cultures and their pertinence for contemporary scientific investigation. Cannabis historians of the past have provided promising clues to potential treatments for a wide array of currently puzzling medical syndromes including chronic pain, spasticity, cancer, seizure disorders, nausea, anorexia, and infectious disease that remain challenges for 21st century medicine. Information gleaned from the history of cannabis administration in its various forms may provide useful points of departure for research into novel delivery techniques and standardization of cannabis-based medicines that will allow their prescription for treatment of these intractable medical conditions.

How to Make Your Own Hemp Oil - Rick Simpson Calls RabbitHoleCentral

Cancer Patient Speaks Out About Medical Marijuana

CANCER-GATE - The Rick Simpson Story (Part 1 of 6)

A420Nation.com - Cannabis Blogs - Cannabis Legalization and Reasonable Thinking.

A420Nation.com - Cannabis Blogs - Cannabis Legalization and Reasonable Thinking.

We don't need no stinking badges!

On Creativity, Marijuana and "a Butterfly Effect in Thought" | Reality Sandwich

On Creativity, Marijuana and "a Butterfly Effect in Thought" | Reality Sandwich

"The truly creative mind in any field is no more than this: A human creature born abnormally, inhumanly sensitive." [...] "...by some strange, unknown, inward urgency they are not really alive unless they are creating." -- Pearl Buck, Winner of a Nobel Prize in Literature in 1938.
In a blog post last year entitled "Marijuana and Divergent Thinking", Jonah Lehrer explains that many creative
tasks require the cultivation of an "expansive associative net, or what psychologists refer to as a "flat associative hierarchy." What this essentially suggests is that creative people should be able to make far-reaching connections among all sorts of seemingly unrelated ideas, and to not dismiss one possible connection just because it seems far-fetched.
Creativity and insight almost always involve an experience of acute pattern recognition: the eureka moment in whicwe perceive the interconnection between disparate concepts or ideas to reveal something new.
The Imaginary Foundation says that "to understand is to perceive patterns" and this is exactly what all great thinkers have done throughout the ages: they have provided a larger, dot-connecting, aerial view of things that subsumes the previous paradigm. As Richard Metzger has written:
What great minds have done throughout history is provide an aerial view of things. A larger more encompassing view that often subsumes the previous paradigm and then surpasses it in completeness with the vividness of its metaphors. Consider now how the evolving notions of a flat earth, Copernican astronomy and Einsteinian physics have subsequently changed how mankind sees its place in the cosmos, continuously updating the past explanations with something superior.
Media philosopher Marshall McLuhan sets a wonderful example as a patternistic thinker: he saw the electronic global village coming decades before the Internet and interpreted electronic communications as extensions of the human nervous system. He connected the dots. A recent review of Douglas Coupland's McLuhan biography said:
More than anything, it paints McLuhan as a masterful dot-connector and voracious cross-disciplinary thinker, a curious octopus if you will.
McLuhan, "was a master of pattern recognition," wrote Coupland, "a man who bangs a drum so large that it's only beaten once every hundred years."
This heightened ability to draw connections and novel associations between disparate ideas or objects is the hallmark of creative thinkers, who are always searching for the initial conditions or tools that epiphanies are born from.
I believe that Marijuana is perhaps one of the best cognitive tools for creativity.
 
The Science

In his ScienceBlogs post, Jonah Lehrer points to a paper recently published in Psychiatry Research, which "sheds some light on why smoking weed seems to unleash a stream of loose associations." In order to examine the relationship between marijuana and creativity, the study looked at a phenomenon called "semantic priming," in which, Lehrer describes:
The activation of one word allows us to react more quickly to related words...Interestingly, marijuana seems to induce a state of hyper-priming, in which the reach of semantic priming extends outwards to distantly related concepts.
He cites Vaughan Bell:
As cannabis certainly causes smokers to have freewheeling thoughts, the researchers decided to test whether stoned participants would show the 'hyper-priming' effect...[And indeed they found that]...volunteers who were under the influence of cannabis showed a definite "hyper-priming" tendency, where distant concepts were reacted to more quickly.
Essentially, marijuana can extend the range of our free-associative capacities. It increases the novel ways in which we find connections between ideas, and it also extends the range of ideas that we might somehow relate to one another.
While not surprising, it does offer a scientific validation for what so many artists, philosophers and scientists have been saying for ages: that marijuana is a cognitive catalyst that can trigger heightened free-associative creativity, increased pattern recognition, and insight.
In this short video I explain how marijuana sparks a butterfly effect in thought:
 

The Subjective Effect

"Cannabis is an assassin of referentiality inducing a BUTTERFLY EFFECT in THOUGHT," says Darwin's Pharmacy author Rich Doyle. This effect "de-conditions our thinking" leading to what RealitySandwich.com described as "the really big connectivity ideas arrived at wholly outside the linear steps of argument. These are the gestalt-perceiving, asterism-forming "aha's!" that connect the dots and light up the sky with a new archetypal pattern."
You can see the hyper-priming, free-associative effect at play when Doyle adds that "cannabis induces a parataxis wherein sentences resonate together and summon coherence in the bardos between one statement and other, rather than through explicit semantics."
"...The words-leap-to-mind, one-after-another, of themselves without having to be searched for," adds anthropologist Henry Munn. "It's a phenomenon similar to the automatic dictation of the surrealists except that here the flow of consciousness tends to be coherent: a rational enunciation of meanings."
"...The fluency, the ease, the aptness of expression one becomes capable of are such that one is astounded by the words that issue forth... For the inspired one, it is as if existence were uttering itself through him..."
To quote Khalil Gibran, it feels as if words "come through you but not from you and though they are with you they belong NOT to you." You feel as if you are having a download.
Psychonaut and ecstatic poet Terence McKenna, who described language as an ecstatic activity of signification, wrote
that marijuana "excites vocalization and empowers articulation. It transmutes language into something that is visibly beheld." Indeed it liberates our linguistic straight-jacket.
Perhaps this is why so many artists have enjoyed marijuana's effects.
Charles Baudelaire was fond of hosting "hashish parties" where members of the intelligentsia could use hashish to elicit a very affective 'rhapsodic oratory':
People completely unsuited for word-play will improvise an endless string of puns and wholly improbable idea relationships fit to outdo the ablest masters of this preposterous craft...
Every difficult question that presents a point of contention for theologians, and brings despair to thoughtful men, becomes clear and transparent. Every contradiction is reconciled. Man has surpassed the gods.
Walter Benjamin wrote the book On Hashish where he articulated philosophical "protocols": first person accounts of marijuana intoxication.
Carl Sagan publicly came out saying marijuana often triggered creative outbursts. So too for Richard Feynman and recently there has been evidence that Shakespeare himself was a toker.

Awe
Accompanying this extended, intellectual hyper-priming, what we also gain with marijuana is an enhanced ability to marvel. As described in Darwin's Pharmacy, "...a sense of interior and exterior dissolves in awareness and awe.... There is an upwelling of fresh insight coupled with a feeling of ubiquitous harmony," in the experience. The vision -- which I hasten to point out, is neither "religious" nor "otherworldly" -- feels like a"startling recognition."
This sense of revelation and awe can be illustrated by a tendency to indulge heady thought experiments like this one described in Doyle's book:
"Christopher Uhl reminds us that "while gazing 'up' at a night sky, one in fact hangs off the planet and near the edge of a galaxy, vertiginous, suspended over the infinity of space." 
Uhl then quotes cosmologist Brian Swimme:
As you lie there feeling yourself hovering within this gravitational bond while peering down at the billions of stars drifting in the infinite chasm of space, you will have entered an experience of the universe that is not just human and not just biological. You will have entered a relationship from a galactic perspective, becoming for a moment a part of the Milky Way galaxy, experiencing what it is like to be the Milky Way galaxy.

 
Marijuana and Art: The 'Ecstasy' of Beauty
"Beauty is an altered stated of consciousness, an extraordinary moment of poetry and grace, a rousing symphonic climax. To seek beauty is to have the willingness, the inclination, and the impetuous desire for this encounter to transpire. Great art expands the way we see. It uplifts the human spirit from the barbaric and thrusts it towards the numinous." -- Director, Imaginary Foundation
"One day we'll fall down and weep and we'll understand it all" -- Tree of Life film.
The sentence above sentence is heard in the trailer to Terrence Malick's Tree of Life and I believe it speaks of the ecstatic illumination bursting forth during our properly understood encounters with great art, great love and great truth.
As I've said before, marijuana enhances our ability to marvel: In some mysterious and uncannily recurring way, marijuana can induce an almost 'synesthetic ecstasy,' whereby a loosening of the usually firm borders that separate our five senses allows for a broader, deeper, more profound, and often time-dilated "interpretation" and "internalization" of moment-to-moment experience.
Marijuana treats us to an awareness of a simultaneity of sensations, a sort of meta-pleasure, which is not surprising, given the roots of the term 'ecstasy,' as Rich Doyle writes:
"Ecstasy" comes etymologically from the experience of "being beside ourselves." The mathematician Brian Rotman has written extensively on this idea that we can experience "parallel" rather than "serial" reality."
This makes it a great tool for the appreciation and study of art.
Imagine the "here and now" as a usually folded accordion, revealing only a fraction of what is there: what weed does is it unfolds this "accordion of the present moment," by sharpening our focus, diverging our thoughts, loosening our reality tunnel, augmenting our semantic priming, removing our judgments and slowing how we perceive time...
Subjectively, this manifests itself in the perception that the "feelings" elicited by art and music are in fact the ACTUAL feelings the artist felt, somehow, dizzyingly "captured" by the work, immortalized, held in "static communion" by the canvas, or musical recording, or camera... and now able to enrapture and enchant us indefinitely.
We FEEL (and correctly recognize) the emotions of the artist, we apprehend the wordless, yet-no-less emotive SENSATIONS that were vividly translated from the artist's inner-experience into a communicable form. It is for this reason that we say that "music communicates the uncommunicable", or that "art is about certain feelings that cannot be expressed accurately in words", or that "a picture is worth a thousand words." We are therefore able to understand art as a tool for communication.
Art may be an important supplement to traditional language, due to its ability to convey and communicate truth that doesn't fit inside the present constraints traditional language might impose on
us.
Perhaps this is why filmmaker Werner Herzog says he prefers "ecstatic truth" to factual truth... For whereas a literal journalist might have certain facts straight, the articulation of a poet or artist, though less "factual", can actually reveal a deeper truth. As Alain DeBotton once wrote, the artist is "willing to sacrifice a naive realism in order to achieve realism of a deeper sort, like a poet who, though less factual than a journalist in describing an event, may nevertheless reveal truths about it that find no place in the other's literal grid."
This still leaves open the question of why the artist chooses to make art. Why doesn't he just "experience the present" and be done with it. It certainly would expend less effort.
Ernest Becker wrote in The Denial Of Death that the artist's motivation comes from a desire to channel the anxiety about our mortality in a creative way. While not disagreeing, I might add that it is when we make art that we defy death.
Richard Doyle explained to me that among other things, a desire to make art "shows that there is compassion, a will to share the outcome of the work of beauty on us, a bubbling desire to awaken us to our common ecstasy. Why suffer when we can SEE?" He continued, saying that insight comes from practice in letting go of prior thought formations and that marijuana does not "cause these sessions but "occasions" them. This is why cannabis must be understood as a teacher plant: if used with intention, we learn to let go of what we "know" and, instead, wonder.
 
Image by Jason White, courtesy of Creative Commons license.

Comments

interesting

that you quote from Khalil's poem "On Children", where he is talking about people's kids (literally or metaphorically, up to you) to talk about what it is like to utter/write words while high i guess that is an example of the 'free-wheeling association' - but please next time be a bit more contextual when you provide a quote, I actually almost assumed he was actually describing what it's like using words while high - but i hadn't heard of him being a big smoker or pot promter, so i had to check it out hate to be a downer, but i think there's a lot of people who while high are not incredibly articulate or creative ... there's a good Dave Chapelle clip on smoking weed: http://www.youtube.com/watch?v=Q2zahZs8GVQ

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brain candy layer cake

Imagination and revelations of the mind are similar to a piece of cake for me. during an epiphany I feel myself biting through the layers of the idea each stubble of realization drops me lower into a state of brilliant understanding. with each layer the realization gets sweeter. with each layer a new taste, a new cream, a new slice of the whole emerges. when you bite into the cake or fully grasp the realization that you are experiencing, you taste all the layers at once. As the layers blend together they create a whole new identity, a whole new meaning as one cohesive entity; or in epiphany terms the "AAH HA!!" moment. so whether you are enjoying an early sunday afternoon epiphany or delicious piece of cake when chewed and digested they both leave you with a hunger for more, wanting to sink into the next layer.

On Creativity, Marijuana and "a Butterfly Effect in Thought"

This is a great article. Thanks.

Dopes

i pretty much deplore people who make cannabis into their lifestyle, if it were a "cognitive tool" it would be one invented by the advertising industry - creativity in service of the dollar, that flattened-associative-hierarchy is an impediment to mastering any skill with vertical depth In fact if you've seen someone ineptly attempt to tie their shoelaces stoned, it seems to degrade existing skill-faculties to an amusing and pathetic degree. Fine for the 'creatives' quickening themselves in the act of creation (what ability did you truly possess yourself if you are reliant on drug-assist?). Now this is a controversial assertion: is it possible reality is perceived in total sobriety ? Another assertion for you "a mirage can never quench the thirst", i think drug intoxication (of any sort) is how many people subconsciously repress their own darkside. And finally, why am i posting to this site you might ask?...i actually enjoy reading this stuff and consider 'spiritual evolution' to be in and of itself an aspirational concept with good intentions and i hope you find what the heart truly wants.

Exploration

I asked myself this same question a few hours ago... Can reality possibly be viewed in complete sobreity. HELL NO it cannot. Just think about the alternate realities and states of consciousness that people have reached outside of your "sober reality." Although i'm not judging you in no manner, i just simply believe the sober life is one of a bounded nature. It is one held in extremely high regard to me for many reasons, but one that is  subject to constant constraint. Assosociations wit the "sober life" and this Earthly reality form a pattern of concrete ideas and thoughts about what the true nature of reality is. But, why would nature provide us with such profound links to other, more unbounded realities? Especially if reality was able to be viewed from only that one perspective, with no other informational agents to help catalyze your natural inclination to experience the Truth. Reality is not possible to be known, it is in accepting that FACT that you truly accept the nature of what reality is. Or at least as i've come to learn it.

What skills?

Well, I can build a house, I spent six months alone in the wilderness, I've turned my whole yard into a garden, I manage a Halloween store, I'm Creative Director for HD Masks, I've written two books the last three years, I maintain a blog, and I smoke every day.
www.offthegridmpls.blogspot.com

Do you think people who take

Do you think people who take adderal or xanax similairly "degrade existing skill-faculties" and "repress their own darkside"?
 
I only ask because I think I sense traces of Nixon-era drug war propaganda. An update since then is that cannabis has already been recognized as a tool, cognitive and otherwise, and not many are claiming it was cooked-up by madison avenue.
 
But I like "creativity in service of the dollar."
People who get to exercise creativity in their jobs are truly lucky. 

associative thought quality and marijuana

OK, I am not in the habit of expressing my experiences of marijuana, except during its experience when in good enough company, and rather, I have trained my brain to express opiates particularities, but in that particularity only particularly for folk who fell into the abuse of that. But here, I have a thought to add. When contemplating marijuana's capacities, in respect of the hyper-priming, free-associative effect, we need evaluate all previous experience.
 
Why one person can associate from bird to plane, and another from bird to feather, depends on a few factors. For example, what are our experiences of witnessing birds, what are our experiences of using the word "bird", and what has our mind previously weeded out of itself as irrelevant to bird life. My brain already weeded big metal objects out as irrelevant to birds, but kept in feathers, as relevant to me, as a decorative and symbolic object I find around me less often than I see feathers in birds. Therefore, when contemplating the worth of marijuana for anybody, we need bear with considerations of how each individual's experiences of it differ, depending upon factors such as how much sanctity we have experienced in our life, for the body, and spirit.
 
For example, men repeatedly bashed and raped in prison, have wildly different kinds of word based associative thinking, from most educated folk. Do we need to read poetry to safely enjoy marijuana? But when it comes to our reading capacity, there is a strong enough difference between indica and sativa, such that we can neither discount/devalue that aspect of the cannabis story. Who is prepared to undertake a clinical study into how the same set of people, maybe differently effected by reading a poem while stoned on cannabis sativa, than when reading a poem while stoned on cannabis indica. (Evaluating the difference between reading aloud and reading silently, can make a difference also.) . . . . .
 
. . . I get it like this in my mind now: a group of pot heads is divided in two groups, and each group is given the same four poems to study, . . . later they get stoned, one subset of people on sativa and the other on indica, and each group reads one poem individually in silence, and one poem aloud to the whole group, but both groups reading the same two poems, . . . then on another day, (preferably two weeks later with no cannabis use in between), they swap around, using the other two poems, and those who first had sativa, now have indica, and those who had indica, have sativa, and then all participants fill out a questionaire for psycho-metric evaluation of their perception of their qualitative experience having been effected by the poems; but now, we also have to repeat the whole experiment, using folk who seldom read, (but are also pot heads), and then we can evaluate something or other about what kind of impact education might be having on the qualitative experiences of pot heads.
 
I suspect it will prove to be a lesson in when less is more.
 
 
when end be nigh
We'll let out the sigh
But that was for real
And the best of all deals
The end that began with each feel
Into death being over and real

the worth of empirical exerimental evidence on marijuana

Yesterday I posted above here, then I got another idea overnight while sleeping, about the parameters of experimental testing of the phenomenon of marijuana enabling hyper-priming free-association, or stream of consciousness thinking, to expand and envelope other ways we think. How about use of marijuana for testing for what it is which defines free-association itself?
 
For example, how strongly will culture influence the patterns in which a mind can freely associate between different words? Do I associate from bird to feather, instead of from bird to aeroplane, because I do not consider “the technocracy” (as defined by Robbie Davis-Floyd), to be a binding culture enabling of me, and rather I enable myself to work within indigenous cultural parameters, in which a bird represents a fear, and a fear in hand is liken to an overcome fear. Is it as simple as acculturative processes, (or instead, as complex as acculturative processes), which free-association is defined by, and what implications does the answer have, for how relevant environmental experiences are to defining the forms of any culture?
 
Further, can cannabis be used to delineate the differences between different cultural bias in how we sequence our communication? For example, when an American associated from bird to aeroplane, was it that he also would associate from feather to bird. Where as an Australian might associate from aeroplane to bird to feather. This is a crude example of what is a common difference in how mainstream American and mainstream Australian ways of communicating differ. The difference originally stems from the extensive influences which indigenous cultures have in the subconscious of anybody living on the lands at which an indigenous initiatory rite tradition is well upkept. Nevada is one such place, as are Australian deserts. The difference is in that native American culture teaches us to approach any fact or theme or event or topic of discussion, by putting our best foot forward, and sustaining ourselves at our best for as long as possible, and then ending by admitting any debt owing to whomsoever we communicated with; whereas indigenous Australian culture, teaches us to start by weeding out all potential grievances, so as that communication can thereafter proceed with real accuracy, and so we always show our shit up front, and hold one another’s worth by how the story proceeds after we’ve waded through all of one another’s shit. The note we finish on is how we are defined in Australia, where as in America, it is the first note in which the clearest self definition takes place. And I am sure that marijuana could be used to investigate this difference, and other similar differences. For example, every culture in the world uses a specific order in what information we divulge to a stranger. What happens when two strangers, from different cultures, meet for the first time, whilst stoned? Do they know whether they will get along if not stoned? Is marijuana enabling or inhibiting of intercultural communication? And why? Why is a substance which can be so opening of the mind, also closing of other potential? That is, the potential to communicate without reliance upon specific word based meaning constructs.
 
Our cultures differ not only in sequencing of communication, but also in that the Americas are home to fire cultures, while Australia is home to one of the world’s water cultures. Native American culture is defined by being situated within the stories most closely associated with the tribe of Judah, while Aboriginal Australian culture is most closely associated in stories, with the tribe of Joseph. Yet these are facts of the matter of our subconscious minds, which are set in a mode of understanding, which prevents our perception outside of the frame of reference of our own culture. We learn to take new regard for our own culture, by becoming acculturated within a different culture also, making it also our own. Would marijuana make culture shock worse or better? How dependent is the positive value of experiencing marijuana, on the company we keep, as well as our previous educational experiences? Is it a negative experience if all those around us are of a different culture to our own? What does this teach us about what any culture is? Sure, we need study and learn about the substances which are commonly available, and psychotropic, so as to promote the best possible outcomes of that availability, but where do we draw the line? We may need to have thorough comprehension of both cannabis indica and cannabis sativa, (guys who’ve spend their lives dealing in it, and are connoisseurs of the different varieties, tend to expect that academics studying the same, no nothing important, and were just all up one another’s asses too far, because they are evaluating their own experientially based know how, above empirical experimental science as defined by modern western European defined cultures), before we could begin to adequately evaluate what effects cannabis can have within intercultural communication contexts. So the question need be, is the experimental work that maybe possible, of real value, and of enough value that it need be conducted? But then again, how have I asked that question without having within myself, a belief that there are folk who already know the answers?
 
The most thorough of material medica books, list as a symptom which cannabis can induce, the inability to know the difference between the imagined and reality. Is it not that this is what psychotropic experiences are all about? Therefore, culture, which defines how we are enabled any imaginative qualities, will always define what feels possible through psychotropic drug taking. I write these words knowing that many may stake a claim in disagreement with me, and they will themselves know, I could just as easily say it will be a cultural difference which is the primary defining factor of their disagreements, and will any of us know any better therefore? Am I a figment of your imagination, or you of mine, and maybe when we use psychotropic substances, the most important point of reference we all need to have, is within our unique individual capacity, to adjoin with a collective subconscious process, in which unity of spirit in humanity, is recognisable as more real than individualised belief. So why do we then feel any need to assert individual assessments of those experiences? No wonder we lend ourselves to false allegations from policing organisations, and no wonder criminalisation of cannabis use occurred in the first place, when individuals talked up in promotion of its use! Talking up about positive experiences of use of cannabis, only enabled “the powers that be” (in the economy), to expect to be able to prove how to gain monetary wealth by blaming the users of cannabis. Is that not what caused its use to become illegal in the first place, (and then caused so many fields to become poisoned with the chemicals used to enable cotton to seem like it could compete with the productivity of hemp). So many questions, and so little empirical experimental evidence!! Or is there?
 
when end be nigh
We'll let out the sigh
But that was for real
And the best of all deals
The end that began with each feel
Into death being over and real

Tis why it's illegal, the

Tis why it's illegal, the drug war is a war on ideology. Of course, aside from the economical, ecological, etc... not so conspirator stories.

Drugs

People are permanently searching for new sensations.the question is: does legal bud get you high ?Marijuana is the most usual drug used nowadays as many teenagers are tented to try it.

I hate to nitpick but the

I hate to nitpick but the statement: "Art may be an important supplement to traditional language..." is inaccurate in its portrayal of the relationship between humans and language. Art is no supplement. Art came first in human cognitive function, we sang before we ever spoke and maybe even painted before we had anything like language. To supplicate art beneath language is to continue a downward trend that serves the aims of cultural empires but does nothing to improve the human condition on our fair planet. Language is used to categorize and commodify and it has done this to music. Language is what allows us to devalue the life work of individual artists as "Not my thing" because they carry the wrong genre-label (or at least any but out preferred label).

Caveat

I thought I'd share my experience with the connection between cannabis and increased cognitive fluidity.
 
After a single instance of smoking, I have definitely experienced what the author speaks of: an expanded network of associations that facilitate creativity. But during periods of regular cannabis use in my life, I've experienced an inverse phenomenon. When I've been smoking a lot, I have a harder time making creative connections in thoughts, speech, humor, etc. Like the opiate abuser who gets hypersensitized to pain, my heavy cannabis use has a cumulative effect that negates the acute effect; it ends up pruning an excess of branches off of my associational networks.
 
From a neural perspective, I would imagine that this correlates with the well-documented decrease in dendritic branching in the hippocampus of heavy cannabis smokers. Less connections in an area of the brain that cobbles together disparate sensory data into episodic memory events sounds likely to lead to a more rigid and regimented thought process.
 
In sum, I find occasional cannabis use to be a crucial wellspring of new connections, but regular use just makes divergent thinking all the more difficult. Anyone with me?

Spot on!

Jason Silva rocks!

How Cannabinoids May Slow Brain Aging | TIME.com

How Cannabinoids May Slow Brain Aging | TIME.com

clipped from article:

Stoners aren’t known for their memory prowess but a new review suggests that drugs similar to marijuana’s active ingredients may hold promise for preventing— or even reversing— brain aging and possibly Alzheimer‘s and other degenerative brain diseases.
Since the mid 2000′s researchers have been building an appreciation for the power of marijuana-like substances that make up the brain’s cannabinoid systems. In animal experiments, for example, synthetic compounds similar to THC—marijuana’s main psychoactive component—have shown promise in preserving brain functions. A 2008 study even demonstrated that a THC-like substance reduced brain inflammation and improved memory in older rats.
MORE: Ballot Initiative of the Day; Will Recreational Marijuana Get the Green Light in Three States?
The latest review, published in Philosophical Transactions of the Royal Society B, suggests that activating the brain’s cannabinoid system may trigger a sort of anti-oxidant cleanse, removing damaged cells and improving the efficiency of the mitochrondria, the energy source that powers cells, ultimately leading to a more robustly functioning brain.
Previous studies have linked cannabinoids to increased amounts of brain-derived neurotrophic factor (BDNF), a substance that protects brain cells and promotes the growth of new ones. Since new cell growth slows or stops during aging, increasing BDNF could potentially slow the decline in cognitive functions.
MORE: Study: Legal Medical Marijuana Doesn’t Encourage Kids to Smoke More Pot
Activation of cannabinoid receptors can also reduce brain inflammation in several different ways, which may in turn suppress some of the disease processes responsible for degenerative brain diseases such as Alzheimer’s.
Andras Bilkei-Gorzo of the Institute of Molecular Psychiatry at the University of Bonn in Germany and an author of the study, is encouraged by the expanding knowledge of the brain’s cannabinoid system and its potential for leading to new understanding of aging in the brain. “[C]annabinoid system activity is neuroprotective,” he wrote, and increasing it “could be a promising strategy for slowing down the progression of brain aging and for alleviating the symptoms of neurodegenerative disorders.”
Still, Gary Wenk, professor of neuroscience, immunology and medical genetics at Ohio State University, who conducted some of the research Bilkei-Gorzo included in the review, is aware of the delicate nature of cannabinoid research, given the controversial nature of medical marijuana issues. “The literature is a mess and he’s done a nice job organizing it,” he says. “He was positive about developing cannabinoid drugs without going overboard.”
VIDEO: Weed Be Gone: Will Amsterdam Ban Pot for Tourists?
Other studies covered in the review showed that mice bred to lack the cannabinoid receptors have better memories early in life but have more rapid cognitive decline as they age, including inflammation in the hippocampus, a key region for memory. “This finding suggests that, at some point during aging, cannabinoid activity helps maintain normal cognitive functions in mice,” says Daniele Piomelli, professor of neurobiology, anatomy and biological chemistry at the University of California – Irvine, who was not associated with the study.
Piomelli cautions that the review doesn’t support the idea of using marijuana to improve brain aging among the elderly, not least because of its psychoactive effects. “This is definitely an important area of investigation but we are still far from a consensus,” he says.
MORE: The Link Between Marijuana and Schizophrenia
Moreover, some of the research covered in the review had conflicting results. Although three clinical trials studied cannabinoids for the treatment of Parkinson's Disease, these studies “did not provide a clear answer whether cannabinoids modify the progression or the outcome of the disease,” wrote Bilkei-Gorzo. He found similar results for Huntington’s Disease, which, like Parkinson’s, is a progressive, degenerative brain disorder. And for the most common form of dementia, “Despite the promising preclinical results, the detailed clinical evaluation of cannabinoids in [Alzheimer's] patients is missing,” he said in the paper.
The social and political challenges to conducting such research, however, mean that it may be a while before we see such scientific gaps filled. Scientists have yet to conduct, for example, a solid study in which they follow marijuana smokers to see if they are more or less likely to develop Alzheimer’s— or to compare the cognitive decline of marijuana smokers to those who do not smoke. Doing so is too controversial to attract funding.
MORE: Medical Marijuana
“In my experience, working in this area is like touching the third rail,” says Wenk, “I get hate and love mails that are bizarre and phone messages from people too high to talk. Some of my colleagues have left the area after seeing their names in the National Enquirer… I do not blame a war on marijuana but rather the public’s prejudice and extreme bias. I’ve now discontinued my research on this system.”
He and others in the field are not completely pessimistic, however. He says, “I’ve been trying to find a drug that will reduce brain inflammation and restore cognitive function in rats for over 25 years; cannabinoids are the first and only class of drugs that have ever been effective. I think that the perception about this drug is changing and in the future people will be less fearful.”
Given that Alzheimer’s already affects one in eight people over 65— and nearly half of those over 85—and there have been few successes at treating or preventing it so far, that would certainly be a welcome change.
(MORE: Outlawing ‘Legal Highs:’ Can Emergency Bans Hinder Drug Development?)

Cannabinoid Receptors as Target for Treatment of Osteoporosis: A Tale of Two Therapies

Cannabinoid Receptors as Target for Treatment of Osteoporosis: A Tale of Two Therapies

clipped from article:

THE SKELETAL ENDOCANNABINOID SYSTEM

Cannabinoids and their Receptor Expression in Bone

A number of recent studies reported that endocannabinoids and their metabolising enzymes are present in the skeleton. AEA and 2-AG are present in the bone marrow and within the metabolically-active trabecular compartment, at levels in the same magnitude as the brain [12, 91]. Both osteoblasts and osteoclasts are capable of producing AEA and 2-AG in culture [12, 91, 92]. Complementary to these findings, a number of cell types within the bone micro-environment including osteoblasts, osteoclasts, osteocytes, stromal cells and adipocytes are found to express the endocannabinoid metabolising enzymes NAPE-phospholipase D, fatty acid amide hydrolyse, diacylglycerol lipases and monoacylgycerol lipase (our unpublished data; [12, 93]). The cannabinoid receptors CB1 and CB2 and a number of closely related receptors and channels such as GPR55 and TRPV1 are found in the skeleton. CB1 receptors are known to be expressed on nerve fibres intervening bone [12, 94] and on cells of the immune system within the BM compartment [2, 30]. We and others reported that CB1 receptors are also detected on osteoblasts, osteoclasts and BM derived adipocytes at both protein and mRNA levels [95, 96]. CB2 receptors on the other hand are highly expressed on peripheral blood mononucleated cells and immune cells including macrophage, monocytes, B and T lymphocytes [26, 30, 97-100]. Osteoblasts, osteoclasts and osteocytes also express CB2 receptors at significantly higher level than that reported for CB1 [31, 32, 93, 96]. Recent studies reported that bone cells also express GPR55 and TRPV1 which are known to be targeted by endocannabinoids and synthetic cannabinoid ligands [36, 96, 101, 102, 111].

Cannabinoid Inverse Agonists/Antagonists as AntiResorptive Agents

The prevention and treatment of excessive bone resorption is based on the use of anti-resorptive agents such as Bisphosphonates and calcitonin. Anti-resorptive drugs are a class of therapeutic agents that selectively/specifically target and inhibit osteoclast differentiation and function with minimal direct activity toward osteoblasts (Reviewed in [103, 104]). We have found that CB1 and CB2 expression on osteoclast and their BM precursor cells is highly up regulated in ageing mice and following oestrogen deficiency in adult mice [95]. To determine the relevance of this finding, we studied the effects of CB1 receptor inactivation on bone loss in ovariectomised mice, a well established model of acute bone loss following oestrogen deficiency [105]. We reported that mice lacking CB1 receptors are protected from ovariectomy-induced bone loss and exhibited reduced osteoclast number and bone resorption in comparison to wild type littermates [32]. We also showed that CB1 deficiency in healthy mice results in accelerated bone growth in neonate and high bone mass in adult mice due to reduced osteoclast number and bone resorption [32]. Surprisingly, the number of osteoblasts and all parameters of bone formation remains unaffected by CB1 deficiency during growth and early adulthood [32, 95]. In contrast, CB2 deficient mice of similar age showed no significant changes in bone mass [31, 106]. Based on these findings, it is clear that CB1 receptors regulate osteoclastic bone resorption in adult mice and that under conditions of increased bone turnover these receptors may regulate bone loss. Interestingly, recent studies have reported that adult mice deficient in the orphan receptor GPR55 display increased peak bone mass due to a significant defect on osteoclastogenesis but the number of osteoblasts remains unaffected [107]. The skeletal abnormalities reported in GPR55 KO mice were remarkably similar to those observed in CB1 deficient mice [32]. Bearing in mind that GPR55 is activated by a number of cannabinoids ligands including endocannabinoids and the CB1 selective agonist AM251 [108, 109], it is likely that GPR55 is involved in the regulation of endocannabinoids action in osteoclastic bone resorption.
Over recent years, we have extensively tested whether pharmacological blockage of cannabinoid receptors may be of value in the prevention of acute bone loss. In our studies, we demonstrated that treatment with the CB1 selective inverse agonist/antagonist AM251 and the CB2 selective inverse agonist/antagonist AM630 reduced osteoclast number and bone resorption in vivo and protected against ovariectomy induced bone loss in adult mice [32, 95]. Other workers reported that the novel CB2 selective antagonist Sch.036 prevented inflammation and bone damage in arthritic mice [110]. Interestingly, genetic inactivation of CB2 receptors in adult mice only partially protected from bone loss due to ovariectomy [106]. This suggests that prevention of bone loss following treatment with CB2 selective inverse agonists/antagonists such as AM630 and Sch.036 may occur at least in part by an effect on CB1 receptors. Nevertheless, these findings together confirm the anti-resorptive capabilities of cannabinoid receptor - in particular CB1 - blockage in animal models of acute bone loss (Fig. 33).
Fig. (3)
Hypothetical model for prevention and treatment of postmenopausal osteoporosis using cannabinoid ligands. Cannabinoid receptors play a role in regulating osteoclast and osteoblast differentiation and activity in the ageing skeleton. ...
A number of in vitro studies have recently shed light on the mechanisms by which cannabinoid receptor blockage regulate osteoclastogenesis. For example, the CB1 selective inverse agonists/antagonists AM251 and Rimonabant© and the CB2 selective inverse agonist/antagonist AM630 are capable of exerting direct inhibitory effects on osteoclast formation, fusion, polarisation and activity [32]. Recent studies in our laboratories demonstrated that cannabinoid receptors also regulate osteoclastogenesis by indirectly influencing “osteoblast-osteoclast coupling” (Fig. 22). For example, we showed that osteoclast formation is significantly reduced in osteoblast – bone marrow co-cultures in which the osteoblasts were prepared from CB1KO mice [95, 106]. Further studies showed that osteoblast cultures generated from CB1KO mice express less RANKL therefore confirming the reduced capabilities of these osteoblast to support osteoclast formation normally [95]. Cannabinoid receptor activation using the endocannabinoids AEA and 2-AG, CB1/2 synthetic agonist CP55,940 and CB2 selective agonist JWH133 and HU308 enhance osteoclast number, increase osteoclast size and multinuclearity and stimulate bone resorption [32, 92, 106]. As with CB1 and CB2 selective agonists, TRPV1 and GPR55 receptor agonists are also capable of increasing osteoclast number in human and mouse cultures [96, 107]. A recent study in our laboratories showed that the TRPV1 agonist capsaicin enhances osteoclast formation, whereas the antagonist capsazepine suppressed osteoclast and osteoblast differentiation and function in vitro and inhibited ovariectomy induced bone loss in mice by reducing indices of bone resorption and bone formation [111]. These results together with earlier findings reported by Rossi and colleagues [96] clearly demonstrate that pharmacological blockade of TRPV1 ion channels is capable of inhibiting osteoclastic bone resorption and as a result protects against bone loss in animal model of osteoporosis [96, 111]. Bearing in mind that cannabinoid receptors, TRPV1 and GPR55 are known to co-exist in a number of cells including osteoclasts and osteoblasts [107, 112-115], it is possible that some of cannabinoids actions may actually be mediated via TRPV1, GPR55 and/or other unknown mechanism(s). In keeping with this, we and others found evidence that activation of CB2 – using the CB2 selective agonists HU308 and ajulemic acid - inhibits osteoclast formation under certain conditions by an unknown mechanism(s) [31, 106, 107, 116]. Regardless of this, it is clear that cannabinoid receptor inverse agonists/antagonists show value as anti-resorptive agents for the prevention of osteoporosis and other bone diseases characterised by increased osteoclast activity (Fig. 33).

Endocannabinoids and Synthetic Cannabinoid Agonists as Bone Anabolic Agents

Bone formation plays a critical role in age-related bone loss and the pathogenesis of a number of bone diseases including postmenopausal and drug-induced osteoporosis [51]. In recent years, extensive research into pathways involved in the regulation of osteoblast differentiation and activity has led to the discovery of a number of bone anabolic agents that stimulate bone formation such as exogenous PTH (also known as teriparatide or Forteo©) (Reviewed in [117]). Endocannabinoids and their receptors are involved in the regulation of osteoblast differentiation and bone formation (Fig. 22). The first evidence supporting a potential effect of cannabinoids on bone formation came from two independent studies examining the role of leptin on food intake and energy metabolism. Ducy et al. showed that leptin, acting on the hypothalamus, influences bone remodelling by negatively regulating bone formation [87]. Complementing this finding, Ravinet et al. reported that genetic inactivation of CB1 receptors reduces leptin levels and body weight in experimental animals [118]. Together these studies suggest that CB1 receptors influence - at least in part - the effects of leptin in osteoblast activity and bone formation (Fig. 22). We and others showed that the endocannabinoids AEA and 2-AG, the synthetic CB1/2 agonist CP55,940 and CB2 selective agonists HU308 and JWH133 stimulate early differentiation of BM derived osteoblast precursors and enhance bone nodule formation in osteoblast cultures in vitro (Fig. 22) [31, 93, 119]. Conversely, treatment with the CB receptor inverse agonist/antagonist AM251 suppresses osteoblast number and function acting on CB1 receptors [95, 106, 119]. We and others also showed that BM stromal cells from CB1 and CB2 deficient mice had a significantly reduced capacity to form mineralised bone nodules when cultured in osteogenic medium and had lower expression of the osteoblast specific alkaline phosphatase and core binding factor alpha1 (Cbfa1) [31, 95], indicating that endocannabinoids and their receptors are capable of exerting a cell autonomous effect on osteoblast and their precursors (Fig. 22).
In most of osteoporotic patients, sustained bone loss is mainly due to significant reduction in osteoblast number and bone formation (Fig. 33) [65, 67]. It was reported that CB2 causes accelerated age-related osteoporosis due to enhanced bone turnover [31]. In our studies however we found that bone loss in ageing CB2 deficient mice is associated with elevated bone resorption coupled to a significant reduction in osteoblast number and bone formation [93]. In agreement with this, activation of the peripherally abundant CB2 receptors, using JWH133 or HU308, protected against bone loss in ovariectomised mice by increasing bone formation markers [31, 93]. These findings - together with evidence showing strong association of CB2 polymorphisms with osteoporosis in women [120, 121] – suggest that CB2 agonists show promise for the treatment of osteoporosis as stimulator of bone formation (Fig. 33). However a recent study using the mouse traumatic brain injury model to investigate the role of cannabinoid receptors in bone formation revealed that CB1 – not CB2 – receptor activation is responsible for increased bone formation following brain injury [12]. The authors of this report went on to suggest that activation of CB1 present on presynaptic nerve endings influence new bone formation by suppressing the release of noradrenaline, an inhibitor of osteoblast activity [12, 122]. Taking into account all findings to date, it is clear that cannabinoid receptor - in particular CB1 - activation regulates osteoblast differentiation and function by directly acting on bone cells and/or indirectly influencing the release of systemic mediators of bone formation such as noradrenaline (Fig. 22).
Encouraged by these findings, we recently investigated the effects of pharmacological and genetic modulation of CB1 receptors on osteoblast differentiation and function in ageing osteoporotic mice. We reported that CB1 deficiency profoundly worsen osteoporosis in 12 month old female mice and resulted in marked loss of bone in male mice of similar age [95]. Detailed histological analysis in our studies showed that CB1 deficiency at this age was associated with a significant reduction in osteoblast number and bone formation resulting in a significant bone loss despite of the significant reduction in osteoclast number (Fig. 33) [32, 95]. This has led us to conclude that age-related osteoporosis associated with CB1 deficiency is not due to increased bone resorption, but is instead due to reduced osteoblast differentiation and bone formation. Osteoporosis in CB1 KO mice was also associated with a striking accumulation of adipocytes in the BM compartment [95]. Studies conducted on bone marrow stromal cells (MSC) – a common precursor to adipocyte and osteoblast - revealed that cultures deficient in CB1 receptors showed a significant reduction in osteoblast differentiation mainly due to an increased capacity of MSC to differentiate into adipocytes [95]. This shift in lineage commitment is coupled to a significant down regulation of the osteoblast specific gene Cbfa1 in osteoblasts and upregulation of cAMP response element binding (CREB) phosphorylation in preadipocytes [95]. All these effects were reproduced pharmacologically in wild type cultures by treating with the CB1 selective inverse agonist/antagonist AM251 [95]. However the pharmacological effects of cannabinoid receptor modulation in adipocyte differentiation reported in the literature are difficult to interpret. For example, endocannabinoids are reported to activate the expression of the adipogenic gene peroxisome proliferator-activated receptor gamma (PPARγ), a powerful stimulator of adipocyte differentiation [123, 124]. Conflicting reports showed that the CB1 selective agonist/inverse antagonist Rimonabant© inhibits cell proliferation but increases markers of adipocyte maturation in preadipocyte cultures [125]. In broad agreement with the latter, we showed that treatment with the CB1 selective agonist/inverse antagonist AM251 inhibits stromal cell differentiation but increases adipocyte differentiation and enhances the expression of adipocyte specific genes such as Fatty acid-binding protein 4, Ccaat-enhancer-binding proteins C/EBPβ and C/EBPα ([95] and Idris et al. unpublished data). Whilst these findings raise the possibility that long term use of cannabinoid receptor inverse agonists/antagonists may suppress osteoblast differentiation and enhance adipogenesis in the bone marrow, they also provide an explanation for the stimulatory effect of cannabinoid agonists on osteoblast activity and bone formation.
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