26 replies to this topic

[birthdaysuit]

Currently: Some days I’m full of energy; blissful and happy, other days I’m completely emotionless, spaced out and anxious. When I’m spaced out my social anxiety goes through the roof. My thoughts can be intrusive, in the way that I overthink social situations sometimes experiencing impending doom. I just want to cry. That’s why I’m so desperately trying to find a cure. I exercise heavily 4 to 5 days a week. I also eat well, quinoa, chia, grains, fruit, vegetables, meat twice a week, fish 2-3 times a week. After, my cannabis induced panic attack I quit cold turkey and started to take various nootropics/adaptogens to live with the burden of social anxiety and situational anxiety.

 

However, I’m back in college with my friends a few of who smoke cannabis religiously. I haven’t smoked cannabis in quite sometime, however, almost everyday I have been near people who are smoking cannabis and I have felt a 2nd hand smoke high. 

 

Until now, I had thought cannabis was the devils lettuce. I was terrified that a small under the breath inhale would spiral me into panic mode. I’m still sure of it. 

 

However, inhaling 2nd hand smoke has done something that I’m sure is not placebo. Over the span of two weeks inhaling small amounts of marijuana (2nd hand style), has lifted the burden of anxiety. For those few hours I feel a great sense of wellbeing, and my intrusive thoughts are all but gone. I’m witty, spontaneous and feel comfortable around anyone. It truly is a godsend!

 

I’m still trying to understand why this is. Because smoking cannabis seemed to have caused my social anxiety. What is cannabis's mechanism of action that helped my body adapt to anxiety??

 

 

 

BACKGROUND - 5 months from present:  I’m 20 years of age, quite smoking cannabis a few months ago and I believe that I have developed a form of social anxiety. All throughout me teenage years, until about a year ago I was an extrovert. Very outgoing, with lots of charisma. However, I am now the complete opposite of that following my cannabis induced panic attack. I have not felt the same since and have become extremely introspective.  

After my cannabis induced panic attack, I quit cold turkey and went to the doctors because I didn’t know who I was. My brain was in a fog, I could not concentrate, my eyesight was blurry and dull almost like I was looking through a film of grey, sounds were earsplitting, I had a full prickly rash all over my body, I had tingling in the fingers and an odd sensation in my left front-upper side of my head that resembled a void/black hole. I always felt it when I smoked but it didn’t seem to bother me until my panic attack. To cope with it I usually try to occupy myself with something or else the sensation will become too overwhelming. Nevertheless, Lyme disease was ruled out, although blood tests can oftentimes come back false negative. My doctor me to take vitamin D3 everyday.  

 

 

 

 

[gamesguru]

THC potently inhibits GABA release^[1]

These results suggest that Delta(9)-THC inhibits GABA release, but does not directly alter GABA(A) receptors or GABA uptake in the hippocampus.

 

So if anything, this mechanism induces effects which are simply anxiogenic.  Call into question therefore, CBD, CBN, CBG, and THCV.

 

THC is also a 5-HT₃ antagonist^[2], see 5-HT(3) receptor antagonists and anxiety; a preclinical and clinical review.

In the short-term, it also boosts dopamine activity, when low dopamine is associated with anxiety^{[3], [source]}.

Here we show that Δ9-tetrahydrocannabinol (THC), the main psychoactive component in cannabis, induces dopamine release in the human striatum. Using the dopamine D₂/D₃ receptor tracer [¹¹C]raclopride and positron emission tomography in seven healthy subjects, we demonstrate that THC inhalation reduces [¹¹C]raclopride binding in the ventral striatum and the precommissural dorsal putamen but not in other striatal subregions. This is consistent with an increase in dopamine levels in these regions. These results suggest that THC shares a potentially addictive property with other drugs of abuse. Further, it implies that the endogenous cannabinoid system is involved in regulating striatal dopamine release...

A comparison of the two sets of images, obtained before and immediately after smoking cannabis, indicated a 20% decrease in the striatal dopamine D₂ receptor binding ratio, suggestive of increased synaptic dopaminergic activity. This observation offers a plausible biological explanation for the psychotogenic effects of cannabis in vulnerable individuals, and also raises speculations about an interaction between cannabinoid and dopaminergic systems in the brain reward pathways.

 

CBD^[4] and THCV^[5] agonise 5-HT_1A, which is a site for novel anxiolytics^[6]

CBD is proposed to activate or modify the function of several receptors in the central nervous system (CNS), including CB1, CB2, GPR55, TRPV1 and 5-HT1A receptors (table 2) [32,33,35,42]. Moreover, it could inhibit the anandamide hydrolysing enzyme (fatty acid amide hydrolase, FAAH) and the adenosine transporter [33,43,50], indirectly increasing the levels of these neurotransmitters.

 

THCV is like the anti-THC, CB1 antagonist, GABA releaser, so forth

The results obtained suggest first, that Δ⁹-THCV can block CB₁-mediated inhibition of GABA release from basket-cell interneurons caused by R-(+)-WIN55212 and second, that by itself Δ⁹-THCV shares the ability of the CB₁ receptor antagonist/inverse agonist, AM251, to increase GABA release from these neurons.

 

Here's a list of non-CB1 or -CB2 related THC actions: http://www.ncbi.nlm....532/table/tbl4/

[gamesguru]

Second-hand smoke though??

CB2:

Cannabinoid-induced upregulation of serotonin 2A receptors in the hypothalamic paraventricular nucleus and anxiety-like behaviors in rats

Here, we studied the effect of a nonselective cannabinoid agonist, CP55940, on the activity of 5-HT2A receptors in hypothalamic paraventricular nucleus (PVN). We detected that repeated exposure to CP55940 enhanced the prolactin and corticosterone neuroendocrine responses mediated by 5-HT2A receptors and increased the membrane-associated levels of 5-HT2A receptors in PVN. Importantly, we also detected increased anxiety-like behaviors in CP55940 treated rats compared to controls. The data presented here suggest that the mechanisms mediating the cannabinoid-induced upregulation of 5-HT2A receptors would be brain-region specific, as we were unable to detect a CP55940-induced upregulation of 5-HT2A mRNA. Our results might provide insight into the molecular mechanism by which repeated exposure to cannabinoids could be associated with the pathophysiology of neuropsychiatric disorders.

 

CB2 receptor agonists upregulate 5-HT2A receptor signaling by activation of the ERK1/2 signaling pathway.

Therefore, these results may provide a molecular mechanism by which activation of cannabinoid receptors might be relevant to the pathophysiology of some cognitive and mood disorders in humans... Activity of cortical 5-HT2A receptors has been associated with several physiological functions and neuropsychiatric disorders such as stress response, anxiety & depression and schizophrenia.

.

Chronic blockade of cannabinoid CB2 receptors induces anxiolytic-like actions associated with alterations in GABA(A) receptors.

Chronic AM630 treatment increased gene and reduced protein expression of CB(2) receptors, GABA(A) α(2) and GABA(A) γ(2) in cortex and amygdala. Chronic JWH133 treatment resulted in opposite gene and protein alterations. In addition, chronic AM630 administration decreased the anxiety of DBA/2 mice in the LDB test.  the efficacy of AM630 in reducing the anxiety of the spontaneously anxious DBA/2 strain of mice strengthens the potential of the CB(2) receptor as a new target in the treatment of anxiety-related disorders

[Ark]

No offense but it seems psychosomatic triggered by core beliefs that have manifested into this social anxiety. My thoughts your genes are kicking in and like many people your starting down the path of early adulthood mood disorder.

[gamesguru]

No offense but it seems psychosomatic triggered by core beliefs that have manifested into this social anxiety. My thoughts your genes are kicking in and like many people your starting down the path of early adulthood mood disorder.

 

In my experience, cannabinoids, especially synthetic and ingested at a young age by someone on the anxiodepressive- or schizo-spectrutm, can really fuck up a person's development, socially, emotionally, financially, and intellectually.

[birthdaysuit]

 

No offense but it seems psychosomatic triggered by core beliefs that have manifested into this social anxiety. My thoughts your genes are kicking in and like many people your starting down the path of early adulthood mood disorder.

 

In my experience, cannabinoids, especially synthetic and ingested at a young age by someone on the anxiodepressive- or schizo-spectrutm, can really fuck up a person's development, socially, emotionally, financially, and intellectually.

 

SO a strain high in CBD’s would help my anxiety??

[gamesguru]

SO a strain high in CBD would help my anxiety??

 

I would expect so[!].  Though it will be $20/day for a 30-50% reduction in symptoms, not 100% cure.  And where to find those strains, or pure CBD?  There's not much supply or demand for it.  That's why I'm first recommending more accessible things like magnesium, kava[!], bacopa, ash, ginkgo, green tea, or even maybe trying st. john's/valerian.

I have already skimmed your newest topic, but will just post here.  Propranolol is a beta-blocker and can be used occasionally against situational anxiety.^{[1], [2], [3]}

I have found natural alpha-blockers^[4], but no natural beta-blockers.

 

More explanations on why cannabis causes more anxiety than it alleviates:

Activation of α4β2*/α6β2* nicotinic receptors alleviates anxiety during nicotine withdrawal without upregulating nicotinic receptors.

Activation of the α7 nicotinic ACh receptor induces anxiogenic effects in rats which is blocked by a 5-HT₁a receptor antagonist.

 

>10microM THC also reduces synaptosomal uptake of anandamide, thereby increasing extracellular concentration

The Endocannabinoid Anandamide Inhibits the Function of α4β2 Nicotinic Acetylcholine Receptors

Differential Effects of Endogenous and Synthetic Cannabinoids on α7-Nicotinic Acetylcholine Receptor-Mediated Responses in Xenopus Oocytes

^^^so perhaps upregulates activity long-term.

 

btw...

A Type-II Positive Allosteric Modulator of α7 nAChRs Reduces Brain Injury and Improves Neurological Function after Focal Cerebral Ischemia in Rats

Characterization of RO5126946, a Novel α7 nicotinic acetylcholine receptor-positive allosteric modulator.

[birthdaysuit]

 

SO a strain high in CBD would help my anxiety??

 

I would expect so[!].  Though it will be $20/day for a 30-50% reduction in symptoms, not 100% cure.  And where to find those strains, or pure CBD?  There's not much supply or demand for it.  That's why I'm first recommending more accessible things like magnesium, kava[!], bacopa, ash, ginkgo, green tea, or even maybe trying st. john's/valerian.

I have already skimmed your newest topic, but will just post here.  Propranolol is a beta-blocker and can be used occasionally against situational anxiety.^{[1], [2], [3]}

I have found natural alpha-blockers^[4], but no natural beta-blockers.

 

More explanations on why cannabis causes more anxiety than it alleviates:

Activation of α4β2*/α6β2* nicotinic receptors alleviates anxiety during nicotine withdrawal without upregulating nicotinic receptors.

Activation of the α7 nicotinic ACh receptor induces anxiogenic effects in rats which is blocked by a 5-HT₁a receptor antagonist.

 

>10microM THC also reduces synaptosomal uptake of anandamide, thereby increasing extracellular concentration

The Endocannabinoid Anandamide Inhibits the Function of α4β2 Nicotinic Acetylcholine Receptors

Differential Effects of Endogenous and Synthetic Cannabinoids on α7-Nicotinic Acetylcholine Receptor-Mediated Responses in Xenopus Oocytes

^^^so perhaps upregulates activity long-term.

 

btw...

A Type-II Positive Allosteric Modulator of α7 nAChRs Reduces Brain Injury and Improves Neurological Function after Focal Cerebral Ischemia in Rats

Characterization of RO5126946, a Novel α7 nicotinic acetylcholine receptor-positive allosteric modulator.

 

Thank you so much,I really appreciate it. So Propranolol would be great for situational anxiety but it obviously comes with some side effects. What would mitigate "fight and flight response,”  does Propranolol do this best?  

Edited by birthdaysuit, 15 September 2015 - 09:11 PM.

[gamesguru]

Side effects include rapid tolerance.

Yes, beta blockers are at least as effective as phenylethanolamine N-methyltransferase inhibitors (which block the conversion of norepinephrine ---> epinephrineine within the medulla of the adrenal gland).

 

Am recommending natural options with cumulative, tolerance-free, even lingering effects.  IME, bacopa and green tea ease approach anxiety!

 

You could try alpha-blockers.

 

 

Inhibitory effect of N(G)-nitro-L-arginine methyl ester on the anti-adrenergic response elicited by ayanin in the pithed rat.

http://www.ncbi.nlm....pubmed/11988855

 

Inhibition of the alpha 1 and alpha 2-adrenoceptor-mediated pressor response in pithed rats by raubasine, tetrahydroalstonine and akuammigine

www.ncbi.nlm.nih.gov/pubmed/6099269

 

Alkaloids and Flavonoids as α1-Adrenergic Receptor Antagonists

http://www.ingentaco...000032/art00004

Edited by gamesguru, 15 September 2015 - 09:26 PM.

[gamesguru]

Chronic Caffeine (8mg/kg) Alters the Density of Adenosine,  Adrenergic , Cholinergic, GABA, and Serotonin Receptors and Calcium Channe ls in Mouse Brain

1. Chronic ingestion of caffeine by male NIH strain mice alters the density of a variety of central receptors.
2. The density of cortical A1 adenosine receptors is increased by 20%, while the density of striatal A2A adenosine receptors is unaltered.
3. The densities of cortical  β1  and  cerebellar β2 adrenergic  receptors are reduced by ca. 25% , while the densities of cortical α1 and α2 adrenergic receptors are not significantly altered. Densities of striatal D1 and D2 dopaminergic receptors are unaltered. The densities of cortical 5 HT1 and 5 HT2 serotonergic receptors are increased by 26–30%. Densities of cortical muscarinic and nicotinic receptors are increased by 40–50%. The density of cortical benzodiazepine-binding sites associated with GABAA receptors is increased by 65%, and the affinity appears slightly decreased. The density of cortical MK-801 sites associated with NMDA-glutaminergic receptors appear unaltered.
4. The density of cortical nitrendipine-binding sites associated with calcium channels is increased by 18%.
5. The results indicate that chronic ingestion of caffeine equivalent to about 100 mg/kg/day in mice causes a wide range of biochemical alterations in the central nervous system.

[birthdaysuit]

 

Chronic Caffeine (8mg/kg) Alters the Density of Adenosine,  Adrenergic , Cholinergic, GABA, and Serotonin Receptors and Calcium Channe ls in Mouse Brain

1. Chronic ingestion of caffeine by male NIH strain mice alters the density of a variety of central receptors.
2. The density of cortical A1 adenosine receptors is increased by 20%, while the density of striatal A2A adenosine receptors is unaltered.
3. The densities of cortical  β1  and  cerebellar β2 adrenergic  receptors are reduced by ca. 25% , while the densities of cortical α1 and α2 adrenergic receptors are not significantly altered. Densities of striatal D1 and D2 dopaminergic receptors are unaltered. The densities of cortical 5 HT1 and 5 HT2 serotonergic receptors are increased by 26–30%. Densities of cortical muscarinic and nicotinic receptors are increased by 40–50%. The density of cortical benzodiazepine-binding sites associated with GABAA receptors is increased by 65%, and the affinity appears slightly decreased. The density of cortical MK-801 sites associated with NMDA-glutaminergic receptors appear unaltered.
4. The density of cortical nitrendipine-binding sites associated with calcium channels is increased by 18%.
5. The results indicate that chronic ingestion of caffeine equivalent to about 100 mg/kg/day in mice causes a wide range of biochemical alterations in the central nervous system.

 

Is this after stopping the consumption of caffeine? I always thought caffeine was harmful to your health.

[gamesguru]

Too much desensitizes receptors, induces tolerance, withdrawal, adrenal fatigue.  Just the right amount gives an energy boost without a crash (especially coadministered with catechins and theanine ... on japanese tea recommendations, see my PM from a few days ago).

 

The control group was given free access to water and food, while the chronic caffeine group was given access to water containing 0.1 % caffeine for 4 days and to food. Caffeine ingestion was continued up to two to four hours before sacrifice.

So, they stopped consumption for 2-4 hrs.  I'm sure given days or weeks, everything would return to near-baseline.

 

It's also just one study, and look they say "Densities of striatal D1 and D2 dopaminergic receptors are unaltered"

Yet a 2015 study found increased striatal D2 from caffeine!  Who to beleive?

[Turnbuckle]

It's possible you have a clinical endocannabinoid deficiency (CECD), which can cause anxiety and a host of symptoms. 

 

http://sensiseeds.co...oid-deficiency/

 

[gamesguru]

Very possible.  We may be onto something if you feel great after toking, exercising^[1], and masturbating^[2].

[Area-1255]

 

THC is also a 5-HT₃ antagonist^[2], see 5-HT(3) receptor antagonists and anxiety; a preclinical and clinical review.

In the short-term, it also boosts dopamine activity, when low dopamine is associated with anxiety^{[3], [source]}. 

 

 

 

Low Dopamine is associated mainly with social anxiety/phobias though - particularly the D2 signaling complex...so a deficiency in D2 concentration and dopamine in general leads to social aversion and isolation. However, there is a precise coordination between D2R-signaling and norepinephrine function and glutamatergic functioning - so it is likely that D(2) activation yields at least some of it's benefits by regulating the AMPA and glutamate responses in these neuron populations and their interneuron excitability. 

There is a strong correlation also, between dopamine D2R function and cholinergic interneuron function - it is brain region dependent - in some area's D2 activation increases acetylcholine release whereas in others it inhibits it. (http://www.sciencedi...006899396013789)

 

(http://www.researchg...rection_in_Rats)

 

http://www.ncbi.nlm....v/pubmed/510357

http://www.sciencedi...00689939090972E

 

Depress Anxiety. 2008;25(1):1-7.

Striatal dopamine D(2) receptor availability in OCD with and without comorbid social anxiety disorder: preliminary findings.

Schneier FR1, Martinez D, Abi-Dargham A, Zea-Ponce Y, Simpson HB, Liebowitz MR, Laruelle M.

Author information

 

Abstract

Dopamine D(2) receptor availability in the striatum has been reported to be low in generalized social anxiety disorder (GSAD) and obsessive-compulsive disorder (OCD), but it has not been studied in persons with comorbid OCD and GSAD (OCD+GSAD). D(2) receptor availability was assessed in 7 subjects with OCD+GSAD, 8 with OCD, and 7 matched healthy comparison (HC) subjects, all unmedicated adults. D(2) receptor availability was assessed with single-photon emission computerized tomography (SPECT) to measure binding potential (BP) of the D(2) receptor radiotracer [(123)I] iodobenzamide ([(123)I]IBZM). Mean striatal [(123)I]IBZM BP was significantly lower in the OCD+GSAD group (72.58 mL/g, SD=18.17) than in the HC group (118.41 mL/g, SD=45.40; P=.025). Mean BP in the OCD group (93.08 mL/g, SD=36.90) did not differ significantly from the HC group (P=.247). Trait detachment, as measured by the Detachment subscale of the Karolinska Scales of Personality, was negatively correlated with D(2) availability across all subjects (r(s)= -.55, P=.013). Comorbid GSAD and OCD may be associated with decreased availability of D(2) receptors in the striatum, consistent with prior findings in GSAD. Prior findings of decreased D(2) receptor availability in noncomorbid OCD were not confirmed. Decreased D(2) receptor availability was also associated with trait detachment, supporting prior findings in samples of healthy subjects.

PMID:   17252580   [PubMed - indexed for MEDLINE]

[gamesguru]

Low Dopamine is associated mainly with social anxiety/phobias though - particularly the D2 signaling complex...

 

PTSD/fear/aversion = "phobia"?

Dopamine in amygdala gates limbic processing of aversive stimuli in humans
Dopamine is known to contribute to the amygdala-mediated aversive response, where increased dopamine release can augment amygdala function. Combining fMRI and PET imaging techniques, Kienast et al. present findings that suggest a functional link between anxiety temperament, dopamine storage capacity and emotional processing in the amygdala.

Post-traumatic stress disorder: the neurobiological impact of psychological trauma

There is evidence in humans that exposure to stressors induces mesolimbic DA release, which in turn could modulate HPA axis responses. Whether or not DA metabolism is altered in PTSD remains unclear, though genetic variations in the DA system have been implicated in moderating risk for PTSD (see below). NE, on the other hand, is one of the principal mediators of autonomic stress responses through both central and peripheral mechanisms.
PTSD patients further show increased amygdala responses to general emotional stimuli that are not trauma-associated, such as emotional faces.

 

found this today, which cast me into doubt

Dopamine transporters, D2 receptors, and dopamine release in generalized social anxiety disorder.
Dopamine D2 receptor and dopamine transporter (DAT) availability in the striatum (STR) have each been reported abnormal in generalized social anxiety disorder (GSAD) in studies using single photon emission computerized tomography (SPECT). D2 receptors and DAT have not previously been studied within the same GSAD subjects, however, and prior GSAD studies have not assessed dopamine release or subdivided the STR into functional subregions.
Unmedicated adults with GSAD (N=17) and matched healthy comparison (HC) subjects (N=13) participated in this study. Of these, 15 GSAD and 13 HC subjects completed baseline assessment of D2 receptor availability using positron emission tomography (PET) with the radiotracer [11C]raclopride. Twelve GSAD and 13 HC subjects completed a repeat scan after intravenous administration of d-amphetamine to study dopamine release. Twelve of the GSAD subjects and 10 of the HC subjects also completed SPECT with the radiotracer [123I] methyl 3beta-(4-iodophenyl) tropane-2beta-carboxylate ([123I]beta-CIT) to assess DAT availability.
GSAD and HC groups did not differ significantly in striatal DAT availability, the overall striatal or striatal subregion D2 receptor availability at baseline, or change in D(2) receptor availability after d-amphetamine. Receptor availability and change after d-amphetamine were not significantly associated with severity of social anxiety or trait detachment.
These findings do not replicate previous findings of altered striatal DAT and  D2  receptor availability in GSAD subjects  assessed with SPECT. The differences from results of prior studies may be due to differences in imaging methods or characteristics of samples.

Edited by gamesguru, 19 September 2015 - 02:14 AM.

[Area-1255]

 

Low Dopamine is associated mainly with social anxiety/phobias though - particularly the D2 signaling complex...

 

PTSD/fear/aversion = "phobia"?

Dopamine in amygdala gates limbic processing of aversive stimuli in humans
Dopamine is known to contribute to the amygdala-mediated aversive response, where increased dopamine release can augment amygdala function. Combining fMRI and PET imaging techniques, Kienast et al. present findings that suggest a functional link between anxiety temperament, dopamine storage capacity and emotional processing in the amygdala.

Post-traumatic stress disorder: the neurobiological impact of psychological trauma

There is evidence in humans that exposure to stressors induces mesolimbic DA release, which in turn could modulate HPA axis responses. Whether or not DA metabolism is altered in PTSD remains unclear, though genetic variations in the DA system have been implicated in moderating risk for PTSD (see below). NE, on the other hand, is one of the principal mediators of autonomic stress responses through both central and peripheral mechanisms.
PTSD patients further show increased amygdala responses to general emotional stimuli that are not trauma-associated, such as emotional faces.

 

found this today, which cast me into doubt

Dopamine transporters, D2 receptors, and dopamine release in generalized social anxiety disorder.
Dopamine D2 receptor and dopamine transporter (DAT) availability in the striatum (STR) have each been reported abnormal in generalized social anxiety disorder (GSAD) in studies using single photon emission computerized tomography (SPECT). D2 receptors and DAT have not previously been studied within the same GSAD subjects, however, and prior GSAD studies have not assessed dopamine release or subdivided the STR into functional subregions.
Unmedicated adults with GSAD (N=17) and matched healthy comparison (HC) subjects (N=13) participated in this study. Of these, 15 GSAD and 13 HC subjects completed baseline assessment of D2 receptor availability using positron emission tomography (PET) with the radiotracer [11C]raclopride. Twelve GSAD and 13 HC subjects completed a repeat scan after intravenous administration of d-amphetamine to study dopamine release. Twelve of the GSAD subjects and 10 of the HC subjects also completed SPECT with the radiotracer [123I] methyl 3beta-(4-iodophenyl) tropane-2beta-carboxylate ([123I]beta-CIT) to assess DAT availability.
GSAD and HC groups did not differ significantly in striatal DAT availability, the overall striatal or striatal subregion D2 receptor availability at baseline, or change in D(2) receptor availability after d-amphetamine. Receptor availability and change after d-amphetamine were not significantly associated with severity of social anxiety or trait detachment.
These findings do not replicate previous findings of altered striatal DAT and  D2  receptor availability in GSAD subjects  assessed with SPECT. The differences from results of prior studies may be due to differences in imaging methods or characteristics of samples.

 

I read that study too, but they are using D-Amphetamine as a comparative/facilitative ligand which creates a new variable and distorts the outcome when in contrast to more 'formal' controlled studies.  The other issue - is although I believe in computerized tomography/chromotography and such - I don't think using it in such a small scale study without thoroughly going over 'reactive subjects' places any doubt on the previous studies until this type of study, at least, is replicated or conferred upon when larger groups of volunteer's or subjects are included..so I have my doubts about this one.

[gamesguru]

I read that study too, but they are using D-Amphetamine as a comparative/facilitative ligand which creates a new variable and distorts the outcome when in contrast to more 'formal' controlled studies.  The other issue - is although I believe in computerized tomography/chromotography and such - I don't think using it in such a small scale study without thoroughly going over 'reactive subjects' places any doubt on the previous studies until this type of study, at least, is replicated or conferred upon when larger groups of volunteer's or subjects are included..so I have my doubts about this one.

Am I misinterpreting something?  Maybe they are doing something like converting too much DA to NE, and this causes anxiety without dramatically altering DA concentration or receptor availability?

Again, it is just one study, employing rather questionable techniques.

Dopamine transporters, D2 receptors, and dopamine release in generalized social anxiety disorder.
Dopamine D2 receptor and dopamine transporter (DAT) availability in the striatum (STR) have each been reported abnormal in generalized social anxiety disorder (GSAD) in studies using single photon emission computerized tomography (SPECT). D2 receptors and DAT have not previously been studied within the same GSAD subjects, however, and prior GSAD studies have not assessed dopamine release or subdivided the STR into functional subregions.
Unmedicated adults with GSAD (N=17) and matched healthy comparison (HC) subjects (N=13) participated in this study. Of these, 15 GSAD and 13 HC subjects completed baseline assessment of D2 receptor availability using positron emission tomography (PET) with the radiotracer [11C]raclopride. Twelve GSAD and 13 HC subjects completed a repeat scan after intravenous administration of d-amphetamine to study dopamine release. Twelve of the GSAD subjects and 10 of the HC subjects also completed SPECT with the radiotracer [123I] methyl 3beta-(4-iodophenyl) tropane-2beta-carboxylate ([123I]beta-CIT) to assess DAT availability.
GSAD and HC groups did not differ significantly in striatal DAT availability, the overall striatal or striatal subregion D2 receptor availability at baseline or change in D(2) receptor availability after d-amphetamine. Receptor availability and change after d-amphetamine were not significantly associated with severity of social anxiety or trait detachment.
These findings do not replicate previous findings of altered striatal DAT and  D2  receptor availability in GSAD subjects assessed with SPECT. The differences from results of prior studies may be due to differences in imaging methods or characteristics of samples.

[Area-1255]

Am I misinterpreting something?  Maybe they are doing something like converting too much DA to NE, and this causes anxiety without dramatically altering DA concentration or receptor availability?

Again, it is just one study, employing rather questionable techniques. 

It's a possibility but we don't really know because other assays haven't been conducted and thus we don't know all of the biological conditions as they were ONLY testing those specific proteins/genes...which makes the idea of the study unreliable. If you are trying to find gene alterations or enzymatic, or proteiogenic differences between subgroups of people with 'behavioral differences', chances are ; you'll find 'em, eventually. This does not however, mean that those differences are RESPONSIBLE as they are merely CORRELATIONS until other findings justify CAUSATION or contributions to the etiology/pathophysiology of those conditions/behavioral spectrums...

 

Biologically, yes , norepinephrine contributes more to anxiety; especially overt forms and ESPECIALLY manic episodes; this has been replicated and repeatedly demonstrated not just in direct studies but also with drugs known to decrease norepinephrine in which also are mood stabilizers etc

Plus our extensive knowledge of the adrenal medulla and adrenal hormone release; including with corticosteroids and their direct relation to adrenaline release and threshold shares the finding of a central role in stress related responses...on a cellular, psychological and endocrine level; this remains true..norepinephrine is a HUGE and PROVEN factor in anxiety disorders.

 

With that being said, dopamine does still have to be in proportion with glutamate and one could have extremely high dopamine and not manifest any severe negative effects if the norepinephrine levels are within the low-range of normal..however, SUPER low norepinephrine is no good , either, and tends to manifest as dysautonomia ; e.g low heart rate, orthostatic hypotension and loss of sensory arousal and taste buds etc...

Edited by Area-1255, 19 September 2015 - 03:10 AM.

[birthdaysuit]

No offense but it seems psychosomatic triggered by core beliefs that have manifested into this social anxiety. My thoughts your genes are kicking in and like many people your starting down the path of early adulthood mood disorder.

You might be right. How would I prevent this from happening. I’m going to therapy and I’m going to start CBT, so we will see if that helps. It could be bi-polar disorder, I just really hope it isn’t. 

[birthdaysuit]

Too much desensitizes receptors, induces tolerance, withdrawal, adrenal fatigue.  Just the right amount gives an energy boost without a crash (especially coadministered with catechins and theanine ... on japanese tea recommendations, see my PM from a few days ago).

 

The control group was given free access to water and food, while the chronic caffeine group was given access to water containing 0.1 % caffeine for 4 days and to food. Caffeine ingestion was continued up to two to four hours before sacrifice.

So, they stopped consumption for 2-4 hrs.  I'm sure given days or weeks, everything would return to near-baseline.

 

It's also just one study, and look they say "Densities of striatal D1 and D2 dopaminergic receptors are unaltered"

Yet a 2015 study found increased striatal D2 from caffeine!  Who to beleive?

Oh that’s right I wanted to ask you something.

 

In the description it says this tea is organic- http://www.denstea.c...25-c-70_91.html

 

Nothing here about these being organic but I could be wrong

http://www.zencha.ne...uct/sencha-moe/

http://www.thes-du-j...products_id=276

 

And I am ordering Bacopa, I’ve heard it up-regulates down-regulated GABA receptors I just want to know the lead and arsenic content. Bacopa is known for picking up heavy metals and I can't find a certificate of analysis on NootropicsDepots Bacopa. http://nootropicsdepot.com/bacopa/

 

I also don’t like that it is from CHINA.

Edited by birthdaysuit, 19 September 2015 - 06:56 PM.

[birthdaysuit]

Very possible.  We may be onto something if you feel great after toking, exercising^[1], and masturbating^[2].

Yup, I feel great after toking in only small amounts, preferably high CBD strains and feel absolutely amazing after exercising, especially mountain biking. I mountain bike most days for 10miles and it really calms me down. 

 

On the other hand, when I masturbate I become unmotivated and fatigued. I refrain from masturbating but if I get an urge i’ll spank the one eyed monster no more than once a week. I‘ve gone three months without masturbating/having sex and I felt that my anxiety was slightly lifted, although I dreaded the increased libido. I could not stop popping boners. 

[gamesguru]

You are right, only the one is organic.  These are all three teas I have tried and liked, btw.  In my experience, organic teas tend to be weaker, and I don't think there is much harm in using synthetic fertilizers.  Also in my experience, not all vendors are created equally, but particular strains from the same farmer tend to be relatively consistent year-to-year, so you could eventually find some favorites.

 

jar jar jar, the Chinese Bacopa is full of lots of lead, which makes one loopy.   but I was so to begin with, so I only enjoy it.  it's also full of bacosides, which make one smart, and I was so to begin with, so I only enjoy it.

 

Anxiogenic-like effects of chronic cannabidiol administration in rats.
Several pre-clinical and human-based studies have shown that acutely administered cannabidiol (CBD) can produce anxiolytic-like effects
The present study investigated the effects of chronic administration of CBD on rat behaviour and on the expression of brain proteins.
Male Lister-hooded rats (150-200 g, n = 8 per group) received daily injections of CBD (10 mg/kg, i.p.) for 14 days. The rats were subjected to two behavioural tests: locomotor activity and conditioned emotional response (CER). The expression of brain-derived neurotrophic factor (BDNF), its receptor tyrosine kinase B (Trk B), extracellular signal-regulated kinases (ERK1/2) and phospho-ERK1/2 and the transcription factor cyclic AMP response element binding protein activation (CREB) and phospho-CREB were determined in brain regions such as the frontal cortex and hippocampus using Western immunoblotting.
CBD significantly increased the time spent freezing in the CER test with no effect on locomotor activity. CBD significantly reduced BDNF expression in the hippocampus and frontal cortex with no change in the striatum. In addition, CBD significantly reduced TrkB expression in the hippocampus with a strong trend towards reduction in the striatum but had no effect in the frontal cortex. In the hippocampus, CBD had no effect on ERK1/2 or phospho-ERK2, but in the frontal cortex, CBD significantly reduced phospho-ERK1/2 expression without affecting total ERK.
Chronic administration of CBD produced an anxiogenic-like effect in clear opposition to the acute anxiolytic profile previously reported. In addition, CBD decreased the expression of proteins that have been shown to be enhanced by chronic treatment with antidepressant/anxiolytic drugs.

-----------------------

Dopamine and serotonin: influences on male sexual behavior.
Steroid hormones regulate sexual behavior primarily by slow, genomically mediated effects. These effects are realized, in part, by enhancing the processing of relevant sensory stimuli, altering the synthesis, release, and/or receptors for neurotransmitters in integrative areas, and increasing the responsiveness of appropriate motor outputs. Dopamine has facilitative effects on sexual motivation, copulatory proficiency, and genital reflexes. Dopamine in the nigrostriatal tract influences motor activity; in the mesolimbic tract it activates numerous motivated behaviors, including copulation; in the medial preoptic area (MPOA) it controls genital reflexes, copulatory patterns, and specifically sexual motivation. Testosterone increases nitric oxide synthase in the MPOA; nitric oxide increases basal and female-stimulated dopamine release, which in turn facilitates copulation and genital reflexes. Serotonin (5-HT) is primarily inhibitory, although stimulation of 5-HT(2C) receptors increases erections and inhibits ejaculation, whereas stimulation of 5-HT(1A) receptors has the opposite effects: facilitation of ejaculation and, in some circumstances, inhibition of erection. 5-HT is released in the anterior lateral hypothalamus at the time of ejaculation. Microinjections of selective serotonin reuptake inhibitors there delay the onset of copulation and delay ejaculation after copulation begins. One means for this inhibition is a decrease in dopamine release in the mesolimbic tract.

Lateral hypothalamic serotonin inhibits nucleus accumbens dopamine: implications for sexual satiety.
Dopamine (DA) is released in several brain areas, including the nucleus accumbens (NAcc), before and during copulation in male rats. DA agonists administered into this area facilitate, and DA antagonists inhibit, numerous motivated behaviors, including male sexual behavior. Serotonin (5-HT) is generally inhibitory to male sexual behavior. We reported previously that 5-HT is released in the anterior lateral hypothalamic area (LHA(A)) and that a selective serotonin reuptake inhibitor microinjected into that area delayed and slowed copulation. Our present results, using high temporal resolution microdialysis, (1) confirm previous electrochemical evidence that extracellular levels of DA increase in the NAcc during copulation and decrease during the postejaculatory interval (PEI) and (2) reveal that LHA(A) 5-HT can inhibit both basal and female-elicited DA release in the NAcc. These findings suggest that the neural circuit promoting sexual quiescence during the PEI includes serotonergic input to the anterior LHA, which in turn inhibits DA release in the NAcc. These findings may also provide insights concerning the inhibitory control of other motivated behaviors activated by the NAcc and may have relevance for understanding the sexual side effects common to antidepressant medications.

Edited by gamesguru, 19 September 2015 - 07:16 PM.

[Area-1255]

jar jar jar, the Chinese Bacopa is full of lots of lead, which makes one loopy.   but I was so to begin with, so I only enjoy it.  it's also full of bacosides, which make one smart, and I was so to begin with, so I only enjoy it.

It's also possible that Bacopa; despite increasing serotonin concentrations ; acts as a selective 5-HT(6) antagonist. So thereby mitigating any inhibition of cognition by serotonin by selective interaction with that receptor. Of interest, many new Alzheimer's drugs in development are targeting / aiming to block the serotonin 6 receptor. 

A synergistic herbal composition from bacopa species for management of neurodegenerative disorders and a process of preparation thereof
 

5-HT₆ receptors and Alzheimer's disease

Edited by Area-1255, 19 September 2015 - 09:28 PM.

[Ark]

Considering your situation talk to your doctor about starting lithium and sertraline. On top of that NAC, lions mane and CBD

[birthdaysuit]

Considering your situation talk to your doctor about starting lithium and sertraline. On top of that NAC, lions mane and CBD

Lions Mane caused depressive like symptoms. 

 

So far only myo-inositol, Reishi, CBD and Green Tea help my social inhibition, inositol and CBD being the most noticeable. I’ll give Bacopa a go and continue me exercise routine. 

[gamesguru]

 

Depress Anxiety. 2008;25(1):1-7.

Striatal dopamine D(2) receptor availability in OCD with and without comorbid social anxiety disorder: preliminary findings.

Schneier FR1, Martinez D, Abi-Dargham A, Zea-Ponce Y, Simpson HB, Liebowitz MR, Laruelle M.

Author information

 

Abstract

Dopamine D(2) receptor availability in the striatum has been reported to be low in generalized social anxiety disorder (GSAD) and obsessive-compulsive disorder (OCD), but it has not been studied in persons with comorbid OCD and GSAD (OCD+GSAD). D(2) receptor availability was assessed in 7 subjects with OCD+GSAD, 8 with OCD, and 7 matched healthy comparison (HC) subjects, all unmedicated adults. D(2) receptor availability was assessed with single-photon emission computerized tomography (SPECT) to measure binding potential (BP) of the D(2) receptor radiotracer [(123)I] iodobenzamide ([(123)I]IBZM). Mean striatal [(123)I]IBZM BP was significantly lower in the OCD+GSAD group (72.58 mL/g, SD=18.17) than in the HC group (118.41 mL/g, SD=45.40; P=.025). Mean BP in the OCD group (93.08 mL/g, SD=36.90) did not differ significantly from the HC group (P=.247). Trait detachment, as measured by the Detachment subscale of the Karolinska Scales of Personality, was negatively correlated with D(2) availability across all subjects (r(s)= -.55, P=.013). Comorbid GSAD and OCD may be associated with decreased availability of D(2) receptors in the striatum, consistent with prior findings in GSAD. Prior findings of decreased D(2) receptor availability in noncomorbid OCD were not confirmed. Decreased D(2) receptor availability was also associated with trait detachment, supporting prior findings in samples of healthy subjects.

PMID:   17252580   [PubMed - indexed for MEDLINE]

 

 

Striatal dopamine D(2) receptor availability in OCD with and without comorbid social anxiety disorder: preliminary findings.
Dopamine D(2) receptor availability in the striatum has been reported to be low in generalized social anxiety disorder (GSAD) and obsessive-compulsive disorder (OCD), but it has not been studied in persons with comorbid OCD and GSAD (OCD+GSAD). D(2) receptor availability was assessed in 7 subjects with OCD+GSAD, 8 with OCD, and 7 matched healthy comparison (HC) subjects, all unmedicated adults. D(2) receptor availability was assessed with single-photon emission computerized tomography (SPECT) to measure binding potential (BP) of the D(2) receptor radiotracer [(123)I] iodobenzamide ([(123)I]IBZM). Mean striatal [(123)I]IBZM BP was significantly lower in the OCD+GSAD group (72.58 mL/g, SD=18.17) than in the HC group (118.41 mL/g, SD=45.40; P=.025). Mean BP in the OCD group (93.08 mL/g, SD=36.90) did not differ significantly from the HC group (P=.247). Trait detachment, as measured by the Detachment subscale of the Karolinska Scales of Personality, was negatively correlated with D(2) availability across all subjects (r(s)= -.55, P=.013). Comorbid GSAD and OCD may be associated with decreased availability of D(2) receptors in the striatum, consistent with prior findings in GSAD. Prior findings of decreased D(2) receptor availability in noncomorbid OCD were not confirmed. Decreased D(2) receptor availability was also associated with trait detachment, supporting prior findings in samples of healthy subjects.