Cannabinoids Elicit Antidepressant-Like Behavior

[Sequoiacrone]

Neurobiology of Disease
Cannabinoids Elicit Antidepressant-Like Behavior and Activate Serotonergic Neurons through the Medial Prefrontal Cortex
Francis Rodriguez Bambico,1 Noam Katz,1,2 Guy Debonnel,1 http://www.jneurosci.org/math/link//dagger.gif and Gabriella Gobbi1,2
1Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, Montréal, Quebec, Canada H3A 1A1, and 2Department of Psychiatry, Centre de Recherche Fernand Seguin, Hôpital L.H. Lafontaine, Université de Montréal, Quebec, Canada H1N 3V2
Correspondence should be addressed to Dr. Gabriella Gobbi, Neurobiological Psychiatry Unit, Department of Psychiatry, Research and Training Building, McGill University, 1033 Pine Avenue West, Montréal, Quebec, Canada H3A 1A1. Email: gabriella.gobbi@mcgill.ca (gabriella.gobbi@mcgill.ca)

Preclinical and clinical studies show that cannabis modulates mood and possesses antidepressant-like properties, mediated by the agonistic activity of cannabinoids on central CB1 receptors (CB1Rs). The action of CB1R agonists on the serotonin (5-HT) system, the major transmitter system involved in mood control and implicated in the mechanism of action of antidepressants, remains however poorly understood. In this study, we demonstrated that, at low doses, the CB1R agonist WIN55,212-2 [R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl) methanone mesylate] exerts potent antidepressant-like properties in the rat forced-swim test (FST). This effect is CB1R dependent because it was blocked by the CB1R antagonist rimonabant and is 5-HT mediated because it was abolished by pretreatment with the 5-HT-depleting agent parachlorophenylalanine. Then, using in vivo electrophysiology, we showed that low doses of WIN55,212-2 dose dependently enhanced dorsal raphe nucleus 5-HT neuronal activity through a CB1R-dependent mechanism. Conversely, high doses of WIN55,212-2 were ineffective in the FST and decreased 5-HT neuronal activity through a CB1R-independent mechanism. The CB1R agonist-induced enhancement of 5-HT neuronal activity was abolished by total or medial prefrontocortical, but not by lateral prefrontocortical, transection. Furthermore, 5-HT neuronal activity was enhanced by the local microinjection of WIN55,212-2 into the ventromedial prefrontal cortex (mPFCv) but not by the local microinjection of WIN55,212-2 into the lateral prefrontal cortex. Similarly, the microinjection of WIN55,212-2 into the mPFCv produced a CB1R-dependent antidepressant-like effect in the FST. These results demonstrate that CB1R agonists possess antidepressant-like properties and modulate 5-HT neuronal activity via the mPFCv.

Key words: cannabinoid; CB1 receptor; serotonin; dorsal raphe nucleus; medial prefrontal cortex; depression; forced swim test
Received April 11, 2007; revised Sept. 11, 2007; accepted Sept. 11, 2007.


Correspondence should be addressed to Dr. Gabriella Gobbi, Neurobiological Psychiatry Unit, Department of Psychiatry, Research and Training Building, McGill University, 1033 Pine Avenue West, Montréal, Quebec, Canada H3A 1A1. Email: gabriella.gobbi@mcgill.ca (gabriella.gobbi@mcgill.ca)


Related articles in J. Neurosci.:
Serotonin, the Prefrontal Cortex, and the Antidepressant-Like Effect of Cannabinoids Fabrício A. Moreira
J. Neurosci. 2007 27: 13369-13370. [Full Text] (http://www.jneurosci.org/cgi/content/full/27/49/13369)
For the source and more information:
http://www.jneurosci.org/cgi/content/abstract/27/43/11700?ct

[Sequoiacrone]

Cannabinoids in bipolar affective disorder: a review and discussion of their therapeutic potential

C. H. Ashton

P. B. Moore
P. Gallagher
A. H. Young
Department of Psychiatry, University of Newcastle upon Tyne, Royal Victoria Infirmary, Newcastle upon Tyne, UK Bipolar affective disorder is often poorly controlled by prescribed drugs. Cannabis use is common in patients with this disorder and anecdotal reports suggest that some patients take it to alleviate symptoms of both mania and depression. We undertook a literature review of cannabis use by patients with bipolar disorder and of the neuropharmacological properties of cannabinoids suggesting possible therapeutic effects in this condition. No systematic studies of cannabinoids in bipolar disorder were found to exist, although some patients claim that cannabisrelieves symptoms of mania and/or depression. The cannabinoids http://jop.sagepub.com/math/Dgr.gif9-tetrahydrocannabinol (THC) and cannabidiol (CBD) may exert sedative, hypnotic, anxiolytic, antidepressant, antipsychotic and anticonvulsant effects. Pure synthetic cannabinoids, such as dronabinol and nabilone and specific plant extracts containing THC, CBD, or amixture of the two in known concentrations, are available and can be delivered sublingually. Controlled trials of these cannabinoids as adjunctive medication in bipolar disorder are now indicated.


For source and article see here:
http://jop.sagepub.com/cgi/content/abstract/19/3/293

[Sequoiacrone]

Cannabis use is associated with enhanced cognitive functioning in schizophrenia

Coulston CM, Perdices M, Tennant CC.

Schizophr Res. 2007 Nov;96(1-3):169-84



The neuropsychological correlates of cannabis use in schizophrenia: lifetime abuse/dependence, frequency of use, and recency of use.

Academic Discipline of Psychological Medicine, Northern Clinical School, University of Sydney, New South Wales, Australia. ccoulston@med.usyd.edu.au This study examined the relationship between neuropsychological performance and three different indices of cannabis use in schizophrenia. These indices were DSM-IV lifetime abuse/dependence, frequency of use, and recency of use. Sixty males with schizophrenia/schizoaffective disorder and 17 healthy males were recruited. The two groups were matched for age, years of education, and premorbid IQ. Medical history, substance use, and psychiatric symptoms were assessed. A neuropsychological battery was also administered to assess attention/processing speed, executive functions, memory, and perceptual organisation. Substance use within 24 hours of cognitive assessment was screened by urine analysis, and a range of confounds were controlled. In the schizophrenia group, 44 participants met DSM-IV criteria for lifetime cannabis abuse/dependence. In addition, there were three mutually exclusive frequency-of-cannabis-use subgroups comprising "high" frequency users (n=11), "medium" frequency users (n=7), and "low" frequency users (n=34) over the preceding year. There were also four mutually exclusive recency-of-cannabis-use categories comprising "cannabis abuse/dependence in the past week" (n=11 users), "non-dependent cannabis use in the past week" (n=7 users), "non-dependent cannabis use in the past month, but prior to the past week" (n=7 users), and "non-dependent cannabis use prior to the past month" (n=9 users). The control group performed better than the schizophrenia group in all cognitive domains. Within the schizophrenia group, a larger proportion of participants with lifetime cannabis abuse/dependence demonstrated better performance than those without lifetime abuse/dependence on a component of psychomotor speed. Frequency and recency of cannabis use were also associated with better neuropsychological performance, predominantly in the domains of attention/processing speed and executive functions. In conclusion, cannabis use is associated with enhanced cognitive functioning in schizophrenia. Implications of the results, limitations of the study, and directions for future research are discussed.

[Sequoiacrone]

Natural remedies for psychiatric conditions
by Ethan Russo, MD
Handbook of Psychotropic Herbs (2001)


The Haworth Press, Inc.
10 Alice Street
Binghampton, New York 13904 USA
800-429-6784
sales@haworthpress.com

Softcover, 2001, $29.95, 352 pp.



In the late 1980s the selective serotonin reuptake inhibitors (SSRIs) burst upon the psychiatric landscape, and fueled by massive advertising campaigns, these new "miraculous" drugs for depression began to generate enormous profits from the ensuing parade of pharmaceuticals: fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), fluvoxamine (Luvox), and citalopram (Celexa). A major change in the treatment of psychiatric disorders came with the new drugs: family doctors began to prescribe them--to children as young as four--and today we are seeing the sequelae of suicidal ideation in young people taking these drugs, as well as aggression (most of the school shooters, such as Columbine, were taking one of the SSRIs)

Now that we know the deadly side effects of these drugs, it seems imperative to find alternatives to the SSRIs. Although many people use herbs occasionally, most are unaware of a number of well-researched herbs found to be effective in treating depression, insomnia, dementia and cognitive impairment, anxiety, and obsessive compulsive disorder (OCD). Ethan Russo, MD, author of several books on psychotropic herbs, and a well-known neurologist with vast clinical experience, has remedied this lack with the Handbook of Psychotropic Herbs.

Dr. Russo's books are solidly rooted in scientific data. His analysis of herbal remedies for psychiatric conditions includes history of usage, botany, preparation of extracts, and the newest research, making his Handbook of Psychotropic Herbs a unique and reliable resource for practitioners.

While some books have focused on herbs for specific uses (e.g. men's health, women's health, tonic herbs, etc.), Dr. Russo's book is the first compilation of scientific and clinical data solely on herbs with central nervous system (CNS) effects.

A comprehensive review of each botanical agent is given, with sound advice on the use of safe and effective herbs which are commonly found on the shelves of health food stores, mail-order catalogs, Web sites, and from health practitioners. "Dr. Russo's treatment of St. John's wort (Hypericum perforatum), is one of the most complete reviews of the clinical literature currently available ..." (from the Foreword).

Besides St. John's wort, Dr. Russo suggests 5-Hydroxytryptophan (Griffonia simplicifolia), Licorice (Glycyrrhiza glabra), and Essential Fatty Acids (EFAs) for depression.

For insomnia, the herbs recommended are Valerian (Valeriana officinalis), Passion Flower (Passiflora incarnata), German Chamomile (Matricaria recutita), Roman (English) Chamomile (Chamaemelum nobile), California Poppy (Eschscholzia californica), Hops (Humulus lupulus), Lemon Balm (Melissa officinalis), Scullcap (Scutellaria lateriflora), and Oats (Avena sativa).

The herbs for dementia and cognitive impairment are fewer: Ginkgo (Ginkgo biloba), Gotu Kola (Centella asiatica), and Huperzine (Huperzia serrata).

For anxiety, one herb: Kava-Kava (Piper methysticum).

For OCD, one herb: Marijuana (Cannabis sativa, Cannabis indica). "OCD is marked by an insurmountable preoccupation with fixed ideas, no matter how preposterous, that withstand the patient's best efforts to submerge them through the application of logic. Cannabis, as no other substance yet discovered, allows a person to forget, and to laugh, even at one's own obsessions and compulsions. For OCD, it sounds like just what the doctor ordered."

The last section of Handbook of Psychotropic Herbs consists of nine Clinical Case Studies, illustrating the efficacy of these herbs: Episodic Use of Kava; Case of Dementia Treated with Ginkgo biloba; Head Injury Treated with Ginkgo; (another) Head Injury Treated with Ginkgo; Treatment of Varied Symptoms with 5-HTP; Dementia Treated with Ginkgo; Treatment with a Variety of Herbal Agents; Managing Mania & Obsessive-Compulsive Disorder; and Cases of Treatment with Ginkgo and Kava.

Ethan Russo, MD is a child and adult neurologist at Montana Neurobehavioral Specialists, and is Board-Certified in Neurology with Special Qualification in Child Neurology. He also holds a faculty position in the Department of Pharmaceutical Sciences as an Adjunct Associate Professor at the University of Montana, where "he regularly lectures to undergraduates and graduate students in pharmacy, psychology, sports medicine, interpersonal communications, and physical therapy." For a neurologist with these credentials to advocate herbal treatment of psychiatric disorders, is a notable event. The alternatives to the SSRIs are in place--the medical community only needs the integrity to use them. In the meantime, these safe remedies are available to those who want to avoid pharmaceutical drugs.

[ILLUSTRATION OMITTED]

review by Irene Alleger

COPYRIGHT 2005 The Townsend Letter Group
COPYRIGHT 2005 Gale Group



Distributed without profit to those who have expressed a prior interest in receiving the included information for research and educational purposes

[Sequoiacrone]

Cannabinoids 2008;3(2):8-10
8 © International Association for Cannabis as Medicine
Original article
Treating depression with cannabinoids
Kurt Blass
Lindengasse 27/10, 1070 Vienna, Austria
Abstract
Although a variety of drugs are available for the treatment of depression, therapy is not effective in
all cases and finding alternative options is desirable. Results from animal studies, anecdotal experience
reported by patients using cannabis and observations from clinical studies where cannabinoids
were used in serious diseases suggest an anti-depressive potential of cannabinoid receptor
agonists. From 2003 to 2006, 75 patients suffering from depression, stress and burnout syndrome
were successfully treated in a practice for general medicine with the cannabis ingredient
dronabinol, alone or in combination with other antidepressants. Two case studies will be presented.
The presented observations suggest that dronabinol has an antidepressive potential that can
readily be used in medical practice.
Key words: Depression, burnout, cannabinoid, cannabis, dronabinol
This article can be downloaded, printed and distributed freely for any non-commercial purposes, provided the original work is properly
cited (see copyright info below). Available online at www.cannabis-med.org
Author's address: Kurt Blaas, drblaas@blowdoc.at
Introduction
In several prospective studies, consumption of cannabis
was associated with an increased risk of developing
depression and anxiety, particularly when cannabis had
been used during adolescence [1,2]. There appears to
be less evidence for a correlation between depression
and cannabis use during adulthood [3,4]. On the other
hand, patients have, in numerous surveys and interviews,
reported anti-depressant and anxiolytic effects
of cannabis [5-11]. Patients suffering from a range of
chronic illnesses have reported that they use cannabis
not only to mitigate physical symptoms, such as pain,
nausea and lack of appetite, but also to improve general
well-being and to mitigate anxiety and depression [8-
10,12].
In several clinical studies, during which subjective
parameters were monitored, cannabinoids not only
improved physical symptoms but also improved wellbeing
and produced measurable antidepressant effects
[13-15]. A study by Musty (2002) with healthy volunteers,
smoking cannabis showed a positive correlation
with the ratings on a scale of depression (MMPI), indicating
an antidepressant effect [16]. These indications
of a therapeutic potential of symptoms of depression
encouraged the author to start administering dronabinol
to select patients suffering from depression.

for the entire article please see here:
http://www.letfreedomgrow.com/cmu/depression_2008_02_2.pdf