Canvassing for Opinion - aka "Blairs Brain on Cannabis"

IMHO prohibition sentiment requires inherent addiction to status quo, an incapacity to visualise beyond the here and now and a desperate desire to know others might feel the same... Reform is not revolutionary, rather it is evolutionary. Having survived banging your head against a brick wall the evolutionist relishes having stopped. / Blair

Saturday, March 20, 2010

Progesterone and Pot on Brain Week.

Dooley, the unofficial mascot of Emory UniversityImage via Wikipedia
The Brain Awareness Week public lecture.in the Philip Carter Family Auditorium, Christchurch Art Gallery, by the eminent neuroscientist Professor Donald Stein (Emory University, Atlanta, Georgia) on "Repairing damaged brains: progesterone, a safe treatment, hidden in plain sight".
[March 18th],

Professor Stein  summarised his 27 year journey towards a current, multi-centre US$28 million clinical trial to minimise the effects of acute brain injury. It seems that sex-steroids, especially progesterone, will do the trick – for both men and women. This hormone may also hold promise in many other conditions associated with brain impairment.
 
Near closing of his enthusiastic talk, Donald spoke of the many rats that had paid dearly to advance science.
Which lead into my question later stemming from my research into sexual behavour of canids (and what we have learned from rats), the role of and influence from hormones, and consequent to working with a patient centred research paradigm, the neuroprotective effects associated with endocannabinoids.

Mani et al. identify the molecular target by which THC affects sexual behavior, and unveil a remarkable operative cross talk mechanism between THC and the progesterone and dopamine signaling pathways.




Our studies indicate that THC acts on the CB1 cannabinoid receptor to initiate a signal transduction response that requires both membrane dopamine and intracellular progesterone receptors for effective induction of sexual behavior.  (see Mani et al, Progesterone receptor and dopamine receptors are required in Δ9-tetrahydrocannabinol modulation of sexual receptivity in female rats )

In earlier research post discovery of THC, we thought it was the estrogen receptor. A lot of rats again.
Then about 1988 Howlett et al using a radioisotope demonstrated binding sites in rat brains. Thus the cannabinoid CB1 and CB2 receptors became the focus of novel research.

The further development of medicinal cannabinoids has been challenged with problems. Research has been fettered by fears and prejudices associated with cannabis 'the plant' and big pharma is challenged by the unpatentable herb.
 These include the psychoactivity of cannabinoid CB1 receptor agonists and the lack of availability of highly selective cannabinoid receptor full agonists (for the CB1 or CB2 receptor), as well as problems of pharmacokinetics. Global activation of cannabinoid receptors is usually undesirable, and so enhancement of local endocannabinoid receptor activity with indirect cannabimimetics is an attractive strategy for therapeutic modulation of the endocannabinoid system. However, existing drugs of this type tend to be metabolized by the same enzymes as their target endocannabinoids and are not yet available in a form that is clinically useful.
While we do not entirely understand the action and thus efficacy of ASPRIN, the all to familiar Paracetamol (acetaminophen) effect is by its degradation into an anandamide (an endocannabinoid).

We do know that cannabinoids exert powerful secondary effects post TBI. The modulation breaks the CNS glutamate cascade that results in early cell death. Anti-inflamatory benefits acrue from CB2 modulation. [Cerebral hypoxia–ischemia and middle cerebral artery occlusion induce expression of the cannabinoid CB2 receptor in the brain. Benito, et al, J Neuroscience.]


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