Cannabinoids (via CB1) raise cortisol, lower prolactin

[Kofi]

Delta-9-THC (a CB1 agonist) increases cortisol and decreases prolactin
[PMID 19083209], as this recent abstract indicates. A drop in
cannabinoid signaling might cause prolactin to rise and cortisol to
drop. High prolactin/low cortisol is sometimes seen in autoimmune
conditions and chronic infections. As I've posted before, gut bacteria
help to regulate mu opioid and cannabinoid receptors in the body and
their loss could conceivably contribute to this problem. And it could
be partially or totally reversed by low-dose naltrexone, which
upregulates the mu opioid receptor (and the mu opioid receptor is vital
for cannabinoid signals).

Psychopharmacology (Berl). 2008 Dec 16;
 
The effects of cannabinoids on serum cortisol and prolactin in humans.
Ranganathan M, Braley G, Pittman B, Cooper T, Perry E, Krystal J,
D'Souza DC.
Schizophrenia Biological Research Center, VA Connecticut Healthcare
System, West Haven, CT, USA, ***@yale.edu.

BACKGROUND: Cannabis is one of the most widely used illicit substances,
and there is growing interest in the therapeutic applications of
cannabinoids. While known to modulate neuroendocrine function, the
precise acute and chronic dose-related effects of cannabinoids in humans
are not well-known. Furthermore, the existing literature on the
neuroendocrine effects of cannabinoids is limited by small sample sizes
(n = 6-22), heterogeneous samples with regard to cannabis exposure
(lumping users and nonusers), lack of controlling for chronic cannabis
exposure, differing methodologies, and limited dose-response data.
Delta-9-tetrahydrocannabinol (Delta-9-THC) was hypothesized to produce
dose-related increases in plasma cortisol levels and decreases in plasma
prolactin levels. Furthermore, relative to controls, frequent users of
cannabis were hypothesized to show altered baseline levels of these
hormones and blunted Delta-9-THC-induced changes of these hormones.
MATERIALS AND METHODS: Pooled data from a series of laboratory studies
with multiple doses of intravenous Delta-9-THC in healthy control
subjects (n = 36) and frequent users of cannabis (n = 40) was examined
to characterize the acute, chronic, and acute on chronic effects of
cannabinoids on plasma cortisol and prolactin levels. Hormone levels
were measured before (baseline) and 70 min after administration of each
dose of Delta-9-THC. Data were analyzed using linear mixed models with
+70 min hormonal levels as the dependant variable and baseline hormonal
level as the covariate. RESULTS: At socially relevant doses, Delta-9-THC
raised plasma cortisol levels in a dose-dependent manner but frequent
users showed blunted increases relative to healthy controls. Frequent
users also had lower baseline plasma prolactin levels relative to
healthy controls. CONCLUSIONS: These group differences may be related to
the development of tolerance to the neuroendocrine effects of
cannabinoids. Alternatively, these results may reflect inherent
differences in neuroendocrine function in frequent users of cannabis and
not a consequence of cannabis use.

PMID: 19083209

LDN (low dose naltrexone) enhances cannabinoid-induced analgesia [PMID
16286810]

friendly gut bacteria - lactobacillus acidophilus - found in yoghurt and
probiotics boosts the synthesis of receptors for mu opioids and
cannabinoids (CB1 and CB2) - our natural painkillers - in human and
rodent gut cells; rats given probiotics experienced a 20% increase in
their pain threshold or twice that if they had irritable bowel syndrome;
the analgesic effect was similar to morphine and suggests the
microbiology of the intestinal tract influences our visceral perception
<http://www.newscientist.com/article/dn10808.html>, [PMID 17159985]

low-dose naltrexone (4.5mg daily in the evenings for twelve weeks) was
significantly effective in a clinical trial for Crohn¹s disease; effects
lasted up to four weeks after discontinuation; 89% of the seventeen
responded; 65% achieved remission; the most common side effect was sleep
disturbance, reported in seven patients [PMID 17222320]; low-dose
naltrexone also works for 76% of a group of 42 patients with irritable
bowel syndrome; it improved pain and other symptoms; the mean weekly
number of pain-free days increased from 0.5+/-1 to 1.25+/-2.14 [PMID
17080248]

endocannabinoids affect the neuroendocrine regulation of hormone
secretion, including the hypothalamus-pituitary-adrenal (HPA) axis; mice
lacking cannabinoid receptor type 1 (CB1-/-) have significant
dysregulation of the HPA axis; although circadian HPA axis
responsiveness is preserved, CB1-/- mice have an enhanced circadian
drive on the HPA axis causing elevated plasma corticosterone
concentrations at the onset of the dark as compared with normal mice;
CB1-/- pituitary cells had a significantly higher ACTH secretion
response to CRH and forskolin challenges; both types mice respond to a
high-dose dexamethasone test, but response to low-dose dexamethasone is
influenced by genotype; CB1-/- mice show increased CRH mRNA levels in
the paraventricular nucleus of the hypothalamus but not in other
extrahypothalamic areas like the amygdala and piriform cortex, in which
CB1 and CRH mRNA have been colocalized; CB1-/- mice have selective
glucocorticoid receptor mRNA down-regulation in the CA1 region of the
hippocampus but not in the dentate gyrus or paraventricular nucleus;
mineralocorticoid receptor mRNA expression levels were unchanged in
these brain areas; CB1 deficiency enhances the circadian HPA axis
activity peak and leads to central impairment of glucocorticoid feedback
[PMID 17194743]

[The Ernie Lie Patrol]

Post by Kofi
Delta-9-THC (a CB1 agonist) increases cortisol and decreases prolactin
[PMID 19083209], as this recent abstract indicates.  A drop in
cannabinoid signaling might cause prolactin to rise and cortisol to
drop.  High prolactin/low cortisol is sometimes seen in autoimmune
conditions and chronic infections.  As I've posted before, gut bacteria
help to regulate mu opioid and cannabinoid receptors in the body and
their loss could conceivably contribute to this problem.  And it could
be partially or totally reversed by low-dose naltrexone, which
upregulates the mu opioid receptor (and the mu opioid receptor is vital
for cannabinoid signals).
Psychopharmacology (Berl). 2008 Dec 16;
 
The effects of cannabinoids on serum cortisol and prolactin in humans.
Ranganathan M, Braley G, Pittman B, Cooper T, Perry E, Krystal J,
D'Souza DC.
Schizophrenia Biological Research Center, VA Connecticut Healthcare
BACKGROUND: Cannabis is one of the most widely used illicit substances,
and there is growing interest in the therapeutic applications of
cannabinoids. While known to modulate neuroendocrine function, the
precise acute and chronic dose-related effects of cannabinoids in humans
are not well-known. Furthermore, the existing literature on the
neuroendocrine effects of cannabinoids is limited by small sample sizes
(n = 6-22), heterogeneous samples with regard to cannabis exposure
(lumping users and nonusers), lack of controlling for chronic cannabis
exposure, differing methodologies, and limited dose-response data.
Delta-9-tetrahydrocannabinol (Delta-9-THC) was hypothesized to produce
dose-related increases in plasma cortisol levels and decreases in plasma
prolactin levels. Furthermore, relative to controls, frequent users of
cannabis were hypothesized to show altered baseline levels of these
hormones and blunted Delta-9-THC-induced changes of these hormones.
MATERIALS AND METHODS: Pooled data from a series of laboratory studies
with multiple doses of intravenous Delta-9-THC in healthy control
subjects (n = 36) and frequent users of cannabis (n = 40) was examined
to characterize the acute, chronic, and acute on chronic effects of
cannabinoids on plasma cortisol and prolactin levels. Hormone levels
were measured before (baseline) and 70 min after administration of each
dose of Delta-9-THC. Data were analyzed using linear mixed models with
+70 min hormonal levels as the dependant variable and baseline hormonal
level as the covariate. RESULTS: At socially relevant doses, Delta-9-THC
raised plasma cortisol levels in a dose-dependent manner but frequent
users showed blunted increases relative to healthy controls. Frequent
users also had lower baseline plasma prolactin levels relative to
healthy controls. CONCLUSIONS: These group differences may be related to
the development of tolerance to the neuroendocrine effects of
cannabinoids. Alternatively, these results may reflect inherent
differences in neuroendocrine function in frequent users of cannabis and
not a consequence of cannabis use.
PMID: 19083209
LDN (low dose naltrexone) enhances cannabinoid-induced analgesia [PMID
16286810]
friendly gut bacteria - lactobacillus acidophilus - found in yoghurt and
probiotics boosts the synthesis of receptors for mu opioids and
cannabinoids (CB1 and CB2) - our natural painkillers - in human and
rodent gut cells; rats given probiotics experienced a 20% increase in
their pain threshold or twice that if they had irritable bowel syndrome;
the analgesic effect was similar to morphine and suggests the
microbiology of the intestinal tract influences our visceral perception
<http://www.newscientist.com/article/dn10808.html>, [PMID 17159985]
low-dose naltrexone (4.5mg daily in the evenings for twelve weeks) was
significantly effective in a clinical trial for Crohn¹s disease; effects
lasted up to four weeks after discontinuation; 89% of the seventeen
responded; 65% achieved remission; the most common side effect was sleep
disturbance, reported in seven patients [PMID 17222320]; low-dose
naltrexone also works for 76% of a group of 42 patients with irritable
bowel syndrome; it improved pain and other symptoms; the mean weekly
number of pain-free days increased from 0.5+/-1 to 1.25+/-2.14 [PMID
17080248]
endocannabinoids affect the neuroendocrine regulation of hormone
secretion, including the hypothalamus-pituitary-adrenal (HPA) axis; mice
lacking cannabinoid receptor type 1 (CB1-/-) have significant
dysregulation of the HPA axis; although circadian HPA axis
responsiveness is preserved, CB1-/- mice have an enhanced circadian
drive on the HPA axis causing elevated plasma corticosterone
concentrations at the onset of the dark as compared with normal mice;
CB1-/- pituitary cells had a significantly higher ACTH secretion
response to CRH and forskolin challenges; both types mice respond to a
high-dose dexamethasone test, but response to low-dose dexamethasone is
influenced by genotype; CB1-/- mice show increased CRH mRNA levels in
the paraventricular nucleus of the hypothalamus but not in other
extrahypothalamic areas like the amygdala and piriform cortex, in which
CB1 and CRH mRNA have been colocalized; CB1-/- mice have selective
glucocorticoid receptor mRNA down-regulation in the CA1 region of the
hippocampus but not in the dentate gyrus or paraventricular nucleus;
mineralocorticoid receptor mRNA expression levels were unchanged in
these brain areas; CB1 deficiency enhances the circadian HPA axis
activity peak and leads to central impairment of glucocorticoid feedback
[PMID 17194743]

Ernie's gut has no friendly bacteria.Even they hate him.

[Nomen Nescio]

Post by Kofi
Delta-9-THC (a CB1 agonist) increases cortisol and decreases prolactin
[PMID 19083209], as this recent abstract indicates.  A drop in
cannabinoid signaling might cause prolactin to rise and cortisol to
drop.  High prolactin/low cortisol is sometimes seen in autoimmune
conditions and chronic infections.  As I've posted before, gut bacteria
help to regulate mu opioid and cannabinoid receptors in the body and
their loss could conceivably contribute to this problem.  And it could
be partially or totally reversed by low-dose naltrexone, which
upregulates the mu opioid receptor (and the mu opioid receptor is vital
for cannabinoid signals).
Psychopharmacology (Berl). 2008 Dec 16;
 
The effects of cannabinoids on serum cortisol and prolactin in humans.
Ranganathan M, Braley G, Pittman B, Cooper T, Perry E, Krystal J,
D'Souza DC.
Schizophrenia Biological Research Center, VA Connecticut Healthcare
BACKGROUND: Cannabis is one of the most widely used illicit substances,
and there is growing interest in the therapeutic applications of
cannabinoids. While known to modulate neuroendocrine function, the
precise acute and chronic dose-related effects of cannabinoids in humans
are not well-known. Furthermore, the existing literature on the
neuroendocrine effects of cannabinoids is limited by small sample sizes
(n = 6-22), heterogeneous samples with regard to cannabis exposure
(lumping users and nonusers), lack of controlling for chronic cannabis
exposure, differing methodologies, and limited dose-response data.
Delta-9-tetrahydrocannabinol (Delta-9-THC) was hypothesized to produce
dose-related increases in plasma cortisol levels and decreases in plasma
prolactin levels. Furthermore, relative to controls, frequent users of
cannabis were hypothesized to show altered baseline levels of these
hormones and blunted Delta-9-THC-induced changes of these hormones.
MATERIALS AND METHODS: Pooled data from a series of laboratory studies
with multiple doses of intravenous Delta-9-THC in healthy control
subjects (n = 36) and frequent users of cannabis (n = 40) was examined
to characterize the acute, chronic, and acute on chronic effects of
cannabinoids on plasma cortisol and prolactin levels. Hormone levels
were measured before (baseline) and 70 min after administration of each
dose of Delta-9-THC. Data were analyzed using linear mixed models with
+70 min hormonal levels as the dependant variable and baseline hormonal
level as the covariate. RESULTS: At socially relevant doses, Delta-9-THC
raised plasma cortisol levels in a dose-dependent manner but frequent
users showed blunted increases relative to healthy controls. Frequent
users also had lower baseline plasma prolactin levels relative to
healthy controls. CONCLUSIONS: These group differences may be related to
the development of tolerance to the neuroendocrine effects of
cannabinoids. Alternatively, these results may reflect inherent
differences in neuroendocrine function in frequent users of cannabis and
not a consequence of cannabis use.
PMID: 19083209
LDN (low dose naltrexone) enhances cannabinoid-induced analgesia [PMID
16286810]
friendly gut bacteria - lactobacillus acidophilus - found in yoghurt and
probiotics boosts the synthesis of receptors for mu opioids and
cannabinoids (CB1 and CB2) - our natural painkillers - in human and
rodent gut cells; rats given probiotics experienced a 20% increase in
their pain threshold or twice that if they had irritable bowel syndrome;
the analgesic effect was similar to morphine and suggests the
microbiology of the intestinal tract influences our visceral perception
<http://www.newscientist.com/article/dn10808.html>, [PMID 17159985]
low-dose naltrexone (4.5mg daily in the evenings for twelve weeks) was
significantly effective in a clinical trial for Crohn¹s disease; effects
lasted up to four weeks after discontinuation; 89% of the seventeen
responded; 65% achieved remission; the most common side effect was sleep
disturbance, reported in seven patients [PMID 17222320]; low-dose
naltrexone also works for 76% of a group of 42 patients with irritable
bowel syndrome; it improved pain and other symptoms; the mean weekly
number of pain-free days increased from 0.5+/-1 to 1.25+/-2.14 [PMID
17080248]
endocannabinoids affect the neuroendocrine regulation of hormone
secretion, including the hypothalamus-pituitary-adrenal (HPA) axis; mice
lacking cannabinoid receptor type 1 (CB1-/-) have significant
dysregulation of the HPA axis; although circadian HPA axis
responsiveness is preserved, CB1-/- mice have an enhanced circadian
drive on the HPA axis causing elevated plasma corticosterone
concentrations at the onset of the dark as compared with normal mice;
CB1-/- pituitary cells had a significantly higher ACTH secretion
response to CRH and forskolin challenges; both types mice respond to a
high-dose dexamethasone test, but response to low-dose dexamethasone is
influenced by genotype; CB1-/- mice show increased CRH mRNA levels in
the paraventricular nucleus of the hypothalamus but not in other
extrahypothalamic areas like the amygdala and piriform cortex, in which
CB1 and CRH mRNA have been colocalized; CB1-/- mice have selective
glucocorticoid receptor mRNA down-regulation in the CA1 region of the
hippocampus but not in the dentate gyrus or paraventricular nucleus;
mineralocorticoid receptor mRNA expression levels were unchanged in
these brain areas; CB1 deficiency enhances the circadian HPA axis
activity peak and leads to central impairment of glucocorticoid feedback
[PMID 17194743]

Another fascinating post.

[Ernie Primeau]

Thanks, Kofi. This makes a lot of sense to me. Ernie

[a***@yahoo.fr]

This is another example of the kind damage that antibiotics can do by
wiping out the normal gut flora. The case for (selected) probiotics is
becoming stronger by the day.

Post by Kofi
Delta-9-THC (a CB1 agonist) increases cortisol and decreases prolactin
[PMID 19083209], as this recent abstract indicates.  A drop in
cannabinoid signaling might cause prolactin to rise and cortisol to
drop.  High prolactin/low cortisol is sometimes seen in autoimmune
conditions and chronic infections.  As I've posted before, gut bacteria
help to regulate mu opioid and cannabinoid receptors in the body and
their loss could conceivably contribute to this problem.  And it could
be partially or totally reversed by low-dose naltrexone, which
upregulates the mu opioid receptor (and the mu opioid receptor is vital
for cannabinoid signals).
Psychopharmacology (Berl). 2008 Dec 16;
 
The effects of cannabinoids on serum cortisol and prolactin in humans.
Ranganathan M, Braley G, Pittman B, Cooper T, Perry E, Krystal J,
D'Souza DC.
Schizophrenia Biological Research Center, VA Connecticut Healthcare
BACKGROUND: Cannabis is one of the most widely used illicit substances,
and there is growing interest in the therapeutic applications of
cannabinoids. While known to modulate neuroendocrine function, the
precise acute and chronic dose-related effects of cannabinoids in humans
are not well-known. Furthermore, the existing literature on the
neuroendocrine effects of cannabinoids is limited by small sample sizes
(n = 6-22), heterogeneous samples with regard to cannabis exposure
(lumping users and nonusers), lack of controlling for chronic cannabis
exposure, differing methodologies, and limited dose-response data.
Delta-9-tetrahydrocannabinol (Delta-9-THC) was hypothesized to produce
dose-related increases in plasma cortisol levels and decreases in plasma
prolactin levels. Furthermore, relative to controls, frequent users of
cannabis were hypothesized to show altered baseline levels of these
hormones and blunted Delta-9-THC-induced changes of these hormones.
MATERIALS AND METHODS: Pooled data from a series of laboratory studies
with multiple doses of intravenous Delta-9-THC in healthy control
subjects (n = 36) and frequent users of cannabis (n = 40) was examined
to characterize the acute, chronic, and acute on chronic effects of
cannabinoids on plasma cortisol and prolactin levels. Hormone levels
were measured before (baseline) and 70 min after administration of each
dose of Delta-9-THC. Data were analyzed using linear mixed models with
+70 min hormonal levels as the dependant variable and baseline hormonal
level as the covariate. RESULTS: At socially relevant doses, Delta-9-THC
raised plasma cortisol levels in a dose-dependent manner but frequent
users showed blunted increases relative to healthy controls. Frequent
users also had lower baseline plasma prolactin levels relative to
healthy controls. CONCLUSIONS: These group differences may be related to
the development of tolerance to the neuroendocrine effects of
cannabinoids. Alternatively, these results may reflect inherent
differences in neuroendocrine function in frequent users of cannabis and
not a consequence of cannabis use.
PMID: 19083209
LDN (low dose naltrexone) enhances cannabinoid-induced analgesia [PMID
16286810]
friendly gut bacteria - lactobacillus acidophilus - found in yoghurt and
probiotics boosts the synthesis of receptors for mu opioids and
cannabinoids (CB1 and CB2) - our natural painkillers - in human and
rodent gut cells; rats given probiotics experienced a 20% increase in
their pain threshold or twice that if they had irritable bowel syndrome;
the analgesic effect was similar to morphine and suggests the
microbiology of the intestinal tract influences our visceral perception
<http://www.newscientist.com/article/dn10808.html>, [PMID 17159985]
low-dose naltrexone (4.5mg daily in the evenings for twelve weeks) was
significantly effective in a clinical trial for Crohn¹s disease; effects
lasted up to four weeks after discontinuation; 89% of the seventeen
responded; 65% achieved remission; the most common side effect was sleep
disturbance, reported in seven patients [PMID 17222320]; low-dose
naltrexone also works for 76% of a group of 42 patients with irritable
bowel syndrome; it improved pain and other symptoms; the mean weekly
number of pain-free days increased from 0.5+/-1 to 1.25+/-2.14 [PMID
17080248]
endocannabinoids affect the neuroendocrine regulation of hormone
secretion, including the hypothalamus-pituitary-adrenal (HPA) axis; mice
lacking cannabinoid receptor type 1 (CB1-/-) have significant
dysregulation of the HPA axis; although circadian HPA axis
responsiveness is preserved, CB1-/- mice have an enhanced circadian
drive on the HPA axis causing elevated plasma corticosterone
concentrations at the onset of the dark as compared with normal mice;
CB1-/- pituitary cells had a significantly higher ACTH secretion
response to CRH and forskolin challenges; both types mice respond to a
high-dose dexamethasone test, but response to low-dose dexamethasone is
influenced by genotype; CB1-/- mice show increased CRH mRNA levels in
the paraventricular nucleus of the hypothalamus but not in other
extrahypothalamic areas like the amygdala and piriform cortex, in which
CB1 and CRH mRNA have been colocalized; CB1-/- mice have selective
glucocorticoid receptor mRNA down-regulation in the CA1 region of the
hippocampus but not in the dentate gyrus or paraventricular nucleus;
mineralocorticoid receptor mRNA expression levels were unchanged in
these brain areas; CB1 deficiency enhances the circadian HPA axis
activity peak and leads to central impairment of glucocorticoid feedback
[PMID 17194743]

[Ernie Primeau]

According to the research I do in my own lab, the antibiotics kill the bad
bacteria in the gut also, so it's even Steven. ThreeLac is the best
probiotic on the market.Google it. Ernie

[a***@yahoo.fr]

I don't know specifically about ThreeLac, but no one probiotic can
claim to be the best on the market, because a probiotic can have
different effects and give different results depending on the
patient's pathology, status of gut flora and probiotic strains. In
this case, ThreeLac is specifically marketed for candida infections.

Post by Ernie Primeau
According to the research I do in my own lab, the antibiotics kill the bad
bacteria in the gut also, so it's even Steven. ThreeLac is the best
probiotic on the market.Google it. Ernie

[Kofi]

This establishes yet another means of efficacy for LDN. It may even be
the case that some of these chronic pain/inflammation syndromes are due
more to the loss dopaminergic tone, which regulates immunity and
neurotransmission. It even suggests LDN might work in Parkinson's or
that CB1 might be deficient in Parkinson's. I'll have more to say when
my articles are finished.

J Neurochem. 2009 Feb;108(3):545-51.
 
D2 receptor-mediated inhibition of dopamine release in the rat striatum
in vitro is modulated by CB1 receptors: studies using fast cyclic
voltammetry.

O'Neill C, Evers-Donnelly A, Nicholson D, O'Boyle KM, O'Connor JJ.
UCD School of Biomolecular and Biomedical Science, UCD Conway Institute
of Biomolecular and Biomedical Research, University College Dublin,
Belfield, Dublin 4, Ireland.

Cannabinoid CB(1) receptors are highly expressed in the striatum where
they are known to be co-localized with dopamine D(2) receptors. There is
now strong evidence that cannabinoids modulate dopamine release in the
brain. Using fast cyclic voltammetry, single pulse stimulation (0.1 ms;
10 V) was applied every 5 min and peak dopamine release was measured
with a carbon fibre microelectrode. Application of the D(2) receptor
agonist, quinpirole, inhibited single pulse dopamine overflow in a
concentration-dependent manner (IC(50): 3.25 x 10(-8) M). The CB(1)
receptor agonist WIN55212-2 (WIN; 1 microM) had no effect on single
pulse dopamine release (93.9 +/- 6.6% at 60 min, n = 5) but attenuated
the inhibitory effect of quinpirole (30 nM; quinpirole 39.0 +/- 4.2% vs.
quinpirole + WIN, 48.2 +/- 3.7%, n = 5, p < 0.05). This affect was
antagonized by the CB(1) receptor antagonist
[N-(Piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-p
yrazole-3-carboxamide] (AM-251, 1 microM). Dopamine release evoked by
four pulses delivered at 1 Hz (4P1Hz) and 10 pulses delivered at 5 Hz
(10P5Hz) was significantly inhibited by WIN [72.3 +/- 7.9% control (peak
4 to 1 ratio measurement) and 66.9 +/- 3.8% control (area under the
curve measurement), respectively, p < 0.05; n = 6 for both]. Prior
perfusion of WIN significantly attenuated the effects of quinpirole on
multiple pulse-evoked dopamine release (4P1Hz: quinpirole, 28.4 +/- 4.8%
vs. WIN + quinpirole, 52.3 +/- 1.2%; 10P5Hz: quinpirole, 29.5 +/- 1.3%
vs. WIN + quinpirole, 59.4 +/-7.1%; p < 0.05 for both; n = 6). These
effects were also antagonized by AM-251 (1 microM). This is the first
report demonstrating a functional, antagonistic interaction between
CB(1) receptors and D(2) autoreceptors in regulating rat striatal
dopamine release.

Publication Types:
* Research Support, Non-U.S. Gov't

PMID: 19187091

[Kofi]

Post by Kofi
It even suggests LDN might work in Parkinson's or
that CB1 might be deficient in Parkinson's.

Two publications on point:


Exp Neurol. 2007 Nov;208(1):110-9. Epub 2007 Aug 22.

Comment in:
Exp Neurol. 2008 Jun;211(2):334-8.

Anti-dyskinetic effects of cannabinoids in a rat model of Parkinson's
disease: role of CB(1) and TRPV1 receptors.
* Morgese MG,
* Cassano T,
* Cuomo V,
* Giuffrida A.

Department of Biomedical Sciences, University of Foggia, Viale Luigi
Pinto 1, 71100 Foggia, Italy.

Levodopa is the most commonly prescribed drug for Parkinson's disease
(PD). Although levodopa improves PD symptoms in the initial stages of
the disease, its long-term use is limited by the development of side
effects, including abnormal involuntary movements (dyskinesias) and
psychiatric complications. The endocannabinoid system is emerging as an
important modulator of basal ganglia functions and its pharmacologic
manipulation represents a promising therapy to alleviate
levodopa-induced dyskinesias. Rats with 6-OHDA lesions that are
chronically treated with levodopa develop increasingly severe axial,
limb, locomotor and oro-facial abnormal involuntary movements (AIMs).
Administration of the cannabinoid agonist WIN 55,212-2 attenuated
levodopa-induced axial, limb and oral AIMs dose-dependently via a
CB(1)-mediated mechanism, whereas it had no effect on locomotive AIMs.
By contrast, systemic administration of URB597, a potent FAAH inhibitor,
did not affect AIMs scoring despite its ability to increase anandamide
concentration throughout the basal ganglia. Unlike WIN, anandamide can
also bind and activate transient receptor potential vanilloid type-1
(TRPV1) receptors, which have been implicated in the modulation of
dopamine transmission in the basal ganglia. Interestingly, URB597
significantly decreased all AIMs subtypes only if co-administered with
the TRPV1 antagonist capsazepine. Our data indicate that pharmacological
blockade of TRPV1 receptors unmasks the anti-dyskinetic effects of FAAH
inhibitors and that CB(1) and TRPV1 receptors play opposite roles in
levodopa-induced dyskinesias.

PMID: 17900568 [PubMed - indexed for MEDLINE]

Related Links
* Effects of levodopa on endocannabinoid levels in rat basal ganglia:
implications for the treatment of levodopa-induced dyskinesias. [Eur J
Neurosci. 2003] PMID: 14511339
* Elevation of endocannabinoid levels in the ventrolateral
periaqueductal grey through inhibition of fatty acid amide hydrolase
affects descending nociceptive pathways via both cannabinoid receptor
type 1 and transient receptor potential vanilloid type-1 receptors. [J
Pharmacol Exp Ther. 2006] PMID: 16284279
* Reciprocal changes in vanilloid (TRPV1) and endocannabinoid (CB1)
receptors contribute to visceral hyperalgesia in the water avoidance
stressed rat. [Gut. 2009] PMID: 18936104
* Decreased endocannabinoid levels in the brain and beneficial effects
of agents activating cannabinoid and/or vanilloid receptors in a rat
model of multiple sclerosis. [Neurobiol Dis. 2005] PMID: 16242629
* A role for vanilloid receptor 1 (TRPV1) and endocannabinnoid
signalling in the regulation of spontaneous and L-DOPA induced
locomotion in normal and reserpine-treated rats. [Neuropharmacology.
2006] PMID: 16806299
* See all Related Articles...


Neuropharmacology. 2003 Dec;45(7):954-63. 

Opioid antagonists increase the dyskinetic response to dopaminergic
agents in parkinsonian monkeys: interaction between dopamine and opioid
systems.
* Samadi P,
* Gregoire L,
* Bedard PJ.

Unite de recherche en Neuroscience, Le Centre Hospitalier Universitaire
de Quebec, Pavillon CHUL, 2705 Boulevard Laurier, Sainte-Foy, Quebec G1V
4G2, Canada.

The pathogenesis of levodopa-induced dyskinesias (LID) still remains
obscure. It has been suggested that enhanced opioidergic transmission in
striatal output pathways may play a role in the induction of LID. To
test this hypothesis, we have investigated the effect of different doses
of the opioid receptor antagonists, naloxone and naltrexone on the
dyskinetic response to a D1 agonist SKF 82958, a D2 agonist quinpirole
and L-3,4-dihydroxyphenylalanine (L-Dopa). We have used six female
cynomolgus monkeys rendered parkinsonian by the toxin MPTP and
presenting a stable parkinsonian syndrome. All responded to L-Dopa and
had developed dyskinesias which were manifested with each dose. The
parkinsonian syndrome and dyskinesias were evaluated for each animal and
scored after the treatments. Locomotor activity was measured by an
electronic motility monitoring system. Our results show that
coadministration of naloxone or naltrexone with dopaminergic agents
leads to a significant increase in the severity of dyskinesias without
noticeable effect on the antiparkinsonian efficacy of the treatment.
These results suggest that increased opioidergic transmission in the two
major striatal output pathways in monkeys or humans with LID might be an
attempt to dampen the effect of abnormal dopaminergic stimulation rather
than the cause of dyskinesias.

PMID: 14573388 [PubMed - indexed for MEDLINE]

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