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Endocannabinoids and psychiatric disorders: the road ahead

Endocannabinoids and psychiatric disorders: the road ahead

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Published by TheHallsOfConfusion

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Published by: TheHallsOfConfusion on Nov 30, 2010
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05/24/2013

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Nature – the leading science journal today – opened the New  Year with an editorial entitled “A decade or psychiaty disorders”.The Editor presented a bleak picture o recent advances in researchand treatment. The hope that a single gene or schizophrenia orother mental illnesses will be ound has evaporated into thin air.Most probably these diseases are based on many hundreds o genes that aect various aspects o brain development. Most o the drugs introduced over the last decades have not led to majordisease improvement, but have mostly reduced the side eects o pharmacological treatments. Hence, the Editor concludes that“a deeper understanding o the underlying biology is essential toimprove diagnosis and treatment”.Pharmacological treatments in psychiatry have depended toomuch and or too long on neurotransmitter systems and theiragonists, such as dopamine, which has been known or over 60years. I believe that the endocannabinoid system, more recently discovered and developed may shed new light on the physiologicalbasis o psychiatric diseases and can be a breath o resh air inpsychiatric pharmacy.
Cannabis 
plant preparations have been used over millenniaboth as a medicine and as “a drug that takes away the mind” (asstated in ancient Assyrian clay tablets). Scientic-medical researchon
cannabis 
started about 150 years ago when a British colonialphysician, W.B. O’Shaugnessy, and a French psychiatrist, J.J.Moreau, undertook clinical trials with Indian and North Arican
cannabis 
respectively. The protocols o these trials would bringshudders to any modern regulatory committee, but their resultsare still o considerable interest. O’Shaughessy ound that ethanolextracts (tincture) o 
cannabis 
resin, when administered to patients with rheumatism, tetanus, rabies, inantile convulsions, cholera,vomiting and
delirium tremens 
gave positive results, which led toextensive use in the UK, where Indian
cannabis 
resin was available.It was ound to be useul in neurological diseases, but not indepression. Moreau, in one o the rst publications published onexperimental psychiatry, also recorded that
cannabis 
was not anantidepressant, but in some ‘cases o 
delirium
’ he had encouragingresults. He described cases o ‘temporary insanity’ at the hugedoses o 
cannabis 
administered. This parallels hypomania cases inSouth Arica, described more than a hundred years later, ater useo 
dagga
, which is known today to contain high concentrationso the active constituent, but no cannabidiol.During the early part o the last century some progress wasmade on the chemistry and pharmacology o 
cannabis 
, but asthe chemical picture was still unclear, interest waned. With theidentication in 1964 o 
9
-
 
tetrahydrocannabinol (
9
-THC) asthe active constituent o the plant, the cannabinoid eld caughtthe interest o many research groups and hundreds o papers onthe chemistry, biochemistry, metabolism, and clinical eects o this compound were published. However its mechanism o actionremained unknown or nearly 2 decades. In the mid-1980’s, thepresence o a cannabinoid receptor in the brain was identiedand shortly thereater it was cloned. This was ollowed by theisolation o the major endogenous cannabinoids, anandamide and2-arachidonoyl glycerol, the elucidation o their biosyntheses anddegradations. This clarication o the chemical and biochemicalbackground led to extensive research in a variety o biologicaland clinical elds. We are now in the midst o major advances inphysiology and clinical applications, associated with the actionso the endocannabinoids.Is the endocannabinoid system involved in psychiatric disorders?Most researchers in the elds will say that the answer is positive,but the experimental results are not straightorward. Thereare publications reporting enhancement o clinical symptomsby a specic cannabinoid and others reporting the opposite.Schizophrenia is one such disorder. In a recent report rom Oslo,
cannabis 
use was associated with better neurocognitive unctionin patients with a bipolar disorder, but the opposite was the caseor schizophrenia subjects. Several groups have brought substantialevidence that
cannabis 
abuse is a risk actor or psychosis ingenetically predisposed people and may lead to a worse outcomeo the disease and that the endogenous cannabinoid system itsel is altered in schizophrenia (i.e., increased density o cannabinoidCB
1
receptor binding in corticolimbic regions and enhancedcerebrospinal fuid anandamide levels). Indeed a ‘cannabinoidhypothesis o schizophrenia’ has been suggested alongside the‘dopamine hypothesis’. However, in spite o the huge increase
editorial
Endocannabinoids and psychiatric disorders:
the road ahead 
Endocanabinoides e transtornos psiquiátricos: a estrada à frente
S5
• Revista Brasileira de Psiquiatria • vol 32 • Suppl I • may2010

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