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Permanent brain damage from cannabis ?

cannabis weed pot anxiety anhedonia emotionally numb emotional numbness emotion blunting cannabis damage

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#1 Londonscouser

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Posted 21 September 2015 - 04:19 PM


Hi, so the purpose of this thread is to see if there is any potential help out there from the seemingly intelligent people on this forum. I possess little scientific knowledge relating to the biological mechanisms that have caused the negative symptoms I have experienced. 

 

I am 21 years of age, and have smoked herbal cannabis, mainly strains containing high amounts of THC, everyday, all day, for 5 years. I started abstaining from cannabis nearly 9 weeks ago. The withdrawal symptoms subsided within 2 weeks.

 

Symptoms I feel come from the result of brain damage or alterations in neuronal pathways;

- Severe emotional numbness, I rarely genuinely laugh, and haven't cried for a few years.

- Social anxiety, isn't severe, however I think my issues may be the result of a drug-induced anxiety disorder. I feel like a high-functioning autistic, and due to my emotional detachment, its impossible to relate and connect with people, including my own family members. Often I feel like a social actor, so I give of the appearance of being 'normal'.

 

Yeh, so that's basically it. Before the manifestation of these symptoms, I guess I would describe myself as outgoing, extremely social. Even after these symptoms appeared, I stupidly continued my chronic consumption of cannabis.

 

Any help or input will be greatly appreciated.



#2 jaiho

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Posted 22 September 2015 - 02:19 AM

You still need more time to resensitise your Dopamine receptors. You can assist this process using the MrHappy Uridine stack.

I doubt it would be permanent damage.


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#3 Londonscouser

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Posted 22 September 2015 - 09:12 AM

You still need more time to resensitise your Dopamine receptors. You can assist this process using the MrHappy Uridine stack.

I doubt it would be permanent damage.

 

Thank you very much for your reply. I will certainly be contemplating taking this stack within the next week or so.

Currently i am taking Vitamin B, C, D3, E, magnesium, zinc and fish oil tablets. In the last few days i have also taken ginko biloba and chinese ginseng.

 

I was also wondering if drinking a lot of green tea may be having any sort of negative effects in regards to my recovery ?

 

1 symptom which is persistent, however doesn't have an impact on my daily life, is that of increased sensitivity to sunlight. However im not 100% sure if this could be related to my cannabis consumption.

 

Anyways, thanks again for the input :D



#4 Lancelott

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Posted 25 September 2015 - 03:10 PM

Hey fellow,

I had the exactly same problem. I'm really interest, and following this thread.

But let me just make a question, have you experienced any kind of turbulence in you life before the symptoms appeared?

I mean, do you have idea when it started? exactly? maybe after any bad experience with cannabis or other drugs?

Cause i know exactly when it started on me. I can easily separate myself in 3 guys. The guy before the incident (outgoing, sociable, confident); the guy just after the incident (exactly the opposite); and the guy i've been since i recovered myself (sociable, but not outgoing.. confident but not extremely as it used to be.. kinda serious..).

It took me some time to recover my personality.. But nowadays i still smoke, not daily, and not in high dosages, but sociably..

I still want to stop it completely. But i guess it is not a personality problem any more.

wish you the best.


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#5 Londonscouser

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Posted 25 September 2015 - 07:56 PM

Hey fellow,

I had the exactly same problem. I'm really interest, and following this thread.

But let me just make a question, have you experienced any kind of turbulence in you life before the symptoms appeared?

I mean, do you have idea when it started? exactly? maybe after any bad experience with cannabis or other drugs?

Cause i know exactly when it started on me. I can easily separate myself in 3 guys. The guy before the incident (outgoing, sociable, confident); the guy just after the incident (exactly the opposite); and the guy i've been since i recovered myself (sociable, but not outgoing.. confident but not extremely as it used to be.. kinda serious..).

It took me some time to recover my personality.. But nowadays i still smoke, not daily, and not in high dosages, but sociably..

I still want to stop it completely. But i guess it is not a personality problem any more.

wish you the best.

 

Hey!

Honestly, I can't pinpoint the exact time-frame when the symptoms appeared...I just carried on smoking...

 

Also, I've never done another illegal drug. Only nicotine and rarely alcohol.

 

How long did you previously quit for ? and how long did it take for you to recover your personality ? Also, were you a daily smoker like me ?

 

So far i've quit for 9 weeks...and I've barely seen any improvements.



#6 Lancelott

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Posted 29 September 2015 - 08:31 PM

Yes, i was a daily smoker, in a large dosage.. And what really damaged my personality was an experience with an extremely concentrated acid drop.

But my issues was getting worse every time i smoked..

It took me maybe almost 1 year to feel like normal again.. maybe not feel normal, but accept the new Me!

And during this year i was still smoking, but not daily and in really small dosages..

But i still suffer from side effects when i smoke nowadays.. Before that happened, smoking used to make me more confident, outgoing, and i didn't give a shit about anything..

Now it makes the exactly opposite.. After smoking i get confused, quiet, paranoid, and makes me think about all wrong things i am doing.. not a pleasant experience, but it helped me to evolve as a human being. 

wish you the best fellow!



#7 gamesguru

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Posted 01 October 2015 - 03:27 AM

am taking Vitamin B, C, D3, E, magnesium, zinc and fish oil tablets. In the last few days i have also taken ginko biloba and chinese ginseng.

I was also wondering if drinking a lot of green tea may be having any sort of negative effects in regards to my recovery ? no, it's good.

 

1 symptom which is persistent, however doesn't have an impact on my daily life, is that of increased sensitivity to sunlight. However im not 100% sure if this could be related to my cannabis consumption.

 

post-13945-0-58840700-1443667829.jpgpost-13945-0-35086100-1443669586.jpg

 

 

 

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#8 arska

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Posted 01 October 2015 - 04:17 AM

This site has good common sense information on cannabis and brain:

http://norml.org/com...-a-user-s-guide

 

Information on it's neuroprotective properties:

http://www.ncbi.nlm....pubmed/10863546 

 

,which is also patented by USA Gov:

https://www.google.c...tents/US6630507

 

Kind regards,

 


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#9 gamesguru

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Posted 01 October 2015 - 11:24 AM

Thought about and researched adaptogen's suggestion (in your 'introduce myself' thread), and maybe he's right that social anxiety is the main issue here.

THC induces a release of glutamate and inhibits the release of gaba, and long-term, this can have the effect of potentiating anxiogenic pathways and dampening anxiolytic ones (a sort of undesirable LTP of glutamate and LTD of gaba, which might take months or years to satisfactorily reverse).

Reason it might take so long is due to desensitized glutamate autoreceptors, and overexpressed or sensitized GABA autoreceptors.  Autoreceptors take longer to renormalize or equalize, and tend to get stuck, lodged, or frozen and need a perturbation or driving signal to equalize or break them out of their stable regime.

abstinence from THC (i.e., placebo periods after THC use) was associated with significantly increased ratings of anxiety, depression, and irritability; decreased ratings of quantity and quality of sleep; and decreased food intake.

The brain from top to bottom: Interactive animation on how Cannabis affects GABA and Dopamine

Cannabis-related impairment and social anxiety: The roles of gender and cannabis use motives

 

cannabidoid-recept.gifMOA_cannab.pngCannabis%20retrograde%20messaging%2050pc

 

 

Mucuna contains natural l-dopa, which over time in large quantities, can cause generalized, systemic dopamine downregulation.

 

CDP-choline is decomposed in the brain to choline + cytidine.  The cytidine is then metabolized to uridine, which affects a dopamine release.  Now it's unclear whether long-term this affects a systemic upregulation or downregulation on dopamine reactivity.

I think short-term it will increase activity via increased release, followed by a brief period where the receptors downregulate (calm before the storm), leading to a depletion of dopamine (due to sustained release), which in turn will finally affect an upregulation of receptors and reactivity to above baseline.  Just a guess, could be mistaken.  If it does downregulate long-term, that would fit in accordance with your anecdote.

It also promotes neurite outgrowth, which doesn't sound too shabby.

Dietary uridine-5′-monophosphate supplementation increases potassium-evoked dopamine release and promotes neurite outgrowth in aged rats
Membrane phospholipids like phosphatidylcholine (PC) are required for cellular growth and repair, and specifically for synaptic function. PC synthesis is controlled by cellular levels of its precursor, cytidine-5′-diphosphate choline (CDP-choline), which is produced from cytidine triphosphate (CTP) and phosphocholine. In rat PC12 cells exogenous uridine was shown to elevate intracellular CDP-choline levels, by promoting the synthesis of uridine triphosphate (UTP), which was partly converted to CTP. In such cells uridine also enhanced the neurite outgrowth produced by nerve growth factor (NGF). The present study assessed the effect of dietary supplementation with uridine-5′-monophosphate disodium (UMP-2Na+, an additive in infant milk formulas) on striatal dopamine (DA) release in aged rats. Male Fischer 344 rats consumed either a control diet or one fortified with 2.5% UMP for 6 wk, ad libitum. In vivo microdialysis was then used to measure spontaneous and potassium (K+)-evoked DA release in the right striatum. Potassium (K+)-evoked DA release was significantly greater among UMP-treated rats, i.e., 341±21% of basal levels vs. 283 ± 9% of basal levels in control rats (p<0.05); basal DA release was unchanged. In general, each animal’s K+-evoked DA release correlated with its striatal DA content, measured postmortem. The levels of neurofilament-70 and neurofilament-M proteins, biomarkers of neurite outgrowth, increased to 182±25% (p<0.05) and 221 ± 34% (p<0.01) of control values, respectively, with UMP consumption. Hence, UMP treatment not only enhances membrane phosphatide production but also can modulate two membrane-dependent processes, neurotransmitter release and neurite outgrowth, in vivo.
 

https://books.google...AAQBAJ&pg=PA414

 

 

You could also try ginseng or st. johns, both inhibitors of dopamine-Beta-hydroxylase (which degrades DA→NE).

Antidepressant-like effects of Trichilia catigua (Catuaba) extract: evidence for dopaminergic-mediated mechanisms

  • Acute oral treatment with the extract of T. catigua produced antidepressant-like effects in the forced swimming model in both mice and rats. Anti-immobility actions of T. catigua extract in mice were significantly reversed by haloperidol or by chlorpromazine, but not by pimozide, ketanserin, spiroxatrine or p-chlorophenylalanine. In vitro, T. catigua extract concentration-dependently inhibited the uptake and increased the release of serotonin, and especially of dopamine, from rat brain synaptosomal preparations.

Mucuna[1]

Rhodiola (MAO-B)

^^^all these things I suspect increase dopamine levels and decrease dopamine receptors

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

these are more natural choices, favoring homeostasis and equilibrium (pay special attention to the upregulators of DA receptors)

PKU-Food-Diagram-copy.jpg
Inducers of PH (phenylalanine hydroxylase):

Lamiaceae[1]??

Simple diet[2]

Exercise[3]

Iron[4]

High ORAC foods[5]

 

Inducers of TH (tyrosine hydroxylase):

Horny goat weed[1]

Lithium

Ginkgo

Bacopa[2]

Green tea[3]

 

Upregulators of receptors (dopamine):

Caffeine[1]

Bacopa[2]

Exercise[3]

Antidepressants[4], [5]

 


Edited by gamesguru, 01 October 2015 - 11:38 AM.

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#10 Londonscouser

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Posted 01 October 2015 - 06:15 PM

Once again Gamesguru, your information provides a great insight. 

 

Also i do partially agree that social anxiety is a big factor, however sometimes I'm not so sure, because its never been as overwhelming as it was when i was intoxicated. Although i do mimic symptoms of social anxiety disorder, I have very little fear in talking to strangers, and i generally don't fear participating in any sort of social interactions. Saying this, i do still believe i got some sort of drug-induced anxiety problem but its certainly not severe, but rather more like mild-moderate. 

 

I've also read about people who suffer from social anxiety and co-suffer from emotional numbness...so its quite possible that during the many times i was intoxicated and affected by severe anxiety, my overwhelmed brain decided to induce a 'coping mechanism' in the form of emotional numbness? its just a theory.

 

Today, a slightly embarrassing social interaction increased my anxiety by a lot for at least a few minutes, and even resulted in a physical symptom in the form of perspiration and probably elevated heart rate. I rarely get physical symptoms from my type of anxiety though, and can't remember the last time i did (probably within the last week or 2 though, or maybe i don't notice when i do).

 

To be honest, i find it difficult to comprehend the information you provide, albeit i haven't done any research on the topics due to being extremely busy as of late.

 

I very much doubt I'd ever want to try an antidepressant, however I do have a question regarding exercise. Currently I try and exercise like 4-5 times a week, usually weight-lifting (because im quite skinny and weak). Would cardiovascular exercises be more beneficial in your opinion ?

 

I've never tried substances such as saint johns wort, or bacopa ect. Do you think its worth a shot ? or should i just continue with my vitamins C&E, for anxiety. I have been taking korean ginseng and ginko biloba for at least 2 weeks now.

 

Also the first time i ever tried green tea (about 10 weeks ago), i remember how i felt like no anxiety for approximately 2-3 hours, however green tea no longer has that type of effect on me anymore, but i do still consume it daily.

 

Once again, thanks for your input, its very much appreciated. Soon enough I will spend a few hours researching and digesting all the knowledge you have posted in order to gain a better understanding.

 



#11 gamesguru

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Posted 01 October 2015 - 07:25 PM

Probably the social anxiety existed before cannabis, and is not really drug-induced although perhaps exacerbated or worsened slightly.  As for the numbness, that is probably very drug induced, and I hear it very often and commonly reported in cannabis users (i don't talk have chance to dialogue with many ex-users unfortunately, but there too it seems common), due to depressed corticostriatal gluatmate autoreceptors, or something similar.

Not sure how many of these "numb" co-suffering "socially anxious" people might have another mental illness (schizophreniform), but cannabis can mimic in non-schizophrenics a range of schizo effects, including numbness/anhedonia/blunted affect:

9-THC also produced negative symptoms of schizophrenia which included blunted affect, reduced rapport, lack of spontaneity, psychomotor retardation, and emotional withdrawal. Of note, these schizophrenia-like negative symptoms may have been confounded by the known cataleptic and sedating effects of 9-THC and further, acute pharmacological studies may have limitations in their capacity to “model” negative symptoms. Nevertheless, a persistent “amotivational syndrome” has been described in chronic heavy cannabis users by some [81, 82, 118, 155, 216] but not others [97, 190]. This so-called “amotivational syndrome” is characterized by apathy, amotivation, social withdrawal, narrowing of interests, lethargy, impaired memory, impaired concentration, disturbed judgment, and impaired occupational achievement. The syndrome has resembled the negative symptoms of schizophrenia. However, other drug use, poverty, low socio-economic status, or preexisting psychiatric disorders existing data confound the interpretation of the existing literature.

-------------
Two trials compared exercise to standard care and both found exercise to significantly improve negative symptoms of mental state.  No absolute effects were found for positive symptoms of mental state.

 

I don't have ghastly social anxiety, or fear of strangers.  It's more like I'm afraid if I have to see the person again, then i could really regret making a bad impression.  Like today I asked a girl at the gym for a photo together by the window, not caring about her sweater and sweatpants, she says "Oh no!".

I hobble back to the calf press, dagger in heart, jump on for a set, and I realize on the eccentric contraction my legs are trembling like a shivering diabetic grandma, tho I didn't at any point feel severely anxious, I was definitely moderately anxious, and looking back to the conversation, I did stutter and fumble important words, and probably moments before this is when my heartrate jumped. 

So next time I approach a girl, I will have more fear of saying the wrong/awkward thing/blowing it.  And by trying to let go of anxiety with anxiety, it becomes worse, and takes til the end of time getting worse.  I just try not to worry what others think.  If they think only sociable people are cool, and I'm not sociable, fine: I'm uncool... someone else (with similar anxiety) will embrace my nature, and see my social side.  Especially if it's just mild-moderate, this little self-exercise of not caring, of reminding yourself failures do not ultimately matter... this should remind you fear/uncertainty is foolish and easy to let go off, otherwise it hurts your confidence more and more.  Anyways, I've never date a girl, so I'm way out of my element in this paragraph.

 

I would try some helpful ones.  Bacopa and kava are effective (possibly ash too), herbal, anxiolytic non-benzodiazapines.  Even ginkgo, it's $20 for 100g powder, and you could see if it helped (though tends to be stimulating/anxiogenic)

http://examine.com/topics/anxiety/

I would assume, there is no research or data to corroborate my guess, that cardio induces more BDNF/NMDAR upregulation for the same amount of time, just cause of rest periods, lower heart rate, lower metabolic output in resistance training.  And increased BDNF/NMDA activity are two ways exercise combats psychiatric illness.  Again I would assume in the same time, treadmill upregulates D2 receptors more than resistance training, so you definitely want to include cardio.  But being skinny and only lifting 4 days a week, i wouldn't let cardio cut into my lifting, eg) lift just as often, but include cardio.

I do 20-30mins freeweights followed by 2 miles on the elliptical.  Leg day I usually do just half a mile, plus warmup sets.  I should do standalone cardio sessions too, but I'm bad, and usually what usually happens is I do free weights and skip cardio.

 

As for the tea, it could have just been your mindset wasn't very anxious those 3 hours due to placebo or external factors, it could have been due an unusual quantity of theanine (high quality leaves usually), or a sort of tolerance which has developed.  Not sure.

The acute effects of L-theanine in comparison with alprazolam on anticipatory anxiety in humans.
L-Theanine (delta-glutamylethylamide) is one of the predominant amino acids ordinarily found in green tea, and historically has been used as a relaxing agent. The current study examined the acute effects of L-theanine in comparison with a standard benzodiazepine anxiolytic, alprazolam (Xanax) and placebo on behavioural measures of anxiety in healthy human subjects using the model of anticipatory anxiety (AA). Sixteen healthy volunteers received alprazolam (1 mg), L-theanine (200 mg) or placebo in a double-blind placebo-controlled repeated measures design. The acute effects of alprazolam and L-theanine were assessed under a relaxed and experimentally induced anxiety condition. Subjective self-reports of anxiety including BAI, VAMS, STAI state anxiety, were obtained during both task conditions at pre- and post-drug administrations. The results showed some evidence for relaxing effects of L-theanine during the baseline condition on the tranquil-troubled subscale of the VAMS. Alprazolam did not exert any anxiolytic effects in comparison with the placebo on any of the measures during the relaxed state. Neither L-theanine nor alprazalam had any significant anxiolytic effects during the experimentally induced anxiety state. The findings suggest that while L-theanine may have some relaxing effects under resting conditions, neither L-theanine not alprazolam demonstrate any acute anxiolytic effects under conditions of increased anxiety in the AA model.


#12 Londonscouser

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Posted 01 October 2015 - 07:57 PM

yeh my form of anxiety sounds pretty similar to what you wrote, although i rarely stumble my words and stuff. A few months before i quit cannabis, i had a oral presentation at university, in front of a large group of people and some lecturers, and i done pretty well achieving 80%.   Does smoking exacerbate your anxiety ?

 

I think you are probably right in the sense that i was sometimes shy before my drug-use, however it literally had no impact on my life.

 

In regards to the numbness or extremely reduced feelings, do you think this could be permanent ? or do you think my emotions will probably increase with intensity but may never be as intense as they used to be ? I do understand the numbness for other people could be a result of schizo-spectrum disorders, PTSD, depression, drug-induced and stress-induced

 

Since i've quit weed, i can remember a few times when I've laughed genuinely, and i think im able to laugh only  if I can really relate to the reason that makes me laugh. I think it could have something to do with imagination/creativity...but im not sure.

 

Anyways i got a massive headache at the moment, so ill probably try and go to sleep ! 10 weeks clean today, and looking forwards to the next few months !



#13 sthira

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Posted 01 October 2015 - 08:14 PM

You know, weed gets a bad name sometimes. Like, if you drank a gallon of coffee you'd feel pretty awful and blame the coffee. Or drink five bottles of red wine, then conclude wine sucks. Or eat three pounds of chocolate, chocolate's bad. Eat too much spinach and you'll feel rotten. You get my drift. Just chill with weed -- not too much, man, just enough to find your spot. Be cool about dosage, and everything's fine. Plus, today's strains are really potent. So we all must learn to adapt to that potency.

#14 gamesguru

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Posted 01 October 2015 - 08:23 PM

You know, weed gets a bad name sometimes. Like, if you drank a gallon of coffee you'd feel pretty awful and blame the coffee. Or drink five bottles of red wine, then conclude wine sucks. Or eat three pounds of chocolate, chocolate's bad. Eat too much spinach and you'll feel rotten. You get my drift. Just chill with weed -- not too much, man, just enough to find your spot. Be cool about dosage, and everything's fine. Plus, today's strains are really potent. So we all must learn to adapt to that potency.

 

Just to be clear and precise, how much are you talking here?  Of daily danks, more or less than 0.25, 0.5, 1.0g? Of mids, less than 0.5, 1.0, 2.0g?

It's important cause if you're doing 0.5 mids, I'm doing 2.0, and that's like comparing one cup of coffee to four cups.  Will four cups of coffee induce amotvation and asociality?  Not even a gallon, but seizures and anxiety, sure, just a different class of drugs, a different class of effects (and side effects).  And like people have bad reactions to coffee, some have bad ones to weed.  I don't like this comparison of a xanthine with a cannabinoind.  May as well compare ergolines to opiates.


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#15 sthira

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Posted 02 October 2015 - 01:48 AM

I don't like this comparison of a xanthine with a cannabinoind. May as well compare ergolines to opiates.


You're right, point taken. And yet I was just trying to communicate that weed should be approached cautiously, attentive to strains and dosages, the timing of when and where, how much and why, with whom and what's up emotionally prior to hitting up. All of that really matters, and especially the strain and dosage.

Meanwhile, the title of this thread is harsh; I don't think there's anything in the literature that suggests smoking weed causes permanent brain damage.

#16 Londonscouser

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Posted 02 October 2015 - 10:47 AM

 

I don't like this comparison of a xanthine with a cannabinoind. May as well compare ergolines to opiates.


You're right, point taken. And yet I was just trying to communicate that weed should be approached cautiously, attentive to strains and dosages, the timing of when and where, how much and why, with whom and what's up emotionally prior to hitting up. All of that really matters, and especially the strain and dosage.

Meanwhile, the title of this thread is harsh; I don't think there's anything in the literature that suggests smoking weed causes permanent brain damage.

 

 

You have a valid point, but this thread isn't about consuming in moderation. What's done is done.

 

Like me, I have found many others who have abused cannabis.

For example, there is one moderator on a 'www.cannabisrehab.org', and he states during his abuse, he was "smoking an eighth a day" & "by the time i quit, my memory was shot to bits and i couldn't string a sentence together". Well, you can say there is no damage, however i am certain there is some sort of permanent alteration in neuronal pathways, and 8 years later, he acknowledges he isn't the same person any more. In essence, cannabis severely damaged his cognition. 

 

There are literally thousands of people that are convinced cannabis gave them an anxiety they never felt before.

 

I've also read about people who are more susceptible to depression after chronically abusing cannabis for a certain period.

 

All in all, cannabis is a great substance, and has the potential to improve the lives of millions. My problems are only a result of my abuse. I find that the types of people who get negative effects in the long run, started smoking cannabis a lot when they were adolescents. 



#17 gamesguru

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Posted 02 October 2015 - 01:07 PM

I think that moderator may have other things going against him, like cheetohs and ice cream, like Flex had Ethylphenidate and other random substances going against him.   With my blueberry and broccoli diet I haven't had much problem with my attention (though sometimes I'm holding a thought, trying to sum up a conclusion, when the thought suddenly leaves me and i am left empty minded... this happens very rarely when I am 16+hrs abstinent, then i feel more clear and attentive).   I probably do an eighth every two days, and it's not the most potent, like midsy.

I'm just saying the negative symptoms are most pronounced.   Sure there's inattentiveness and delusions, but these tend to only occur for 24 hours after a huge dose... the negative symptoms are like permanent, eg) quit 3 years, minimal improvement in social skill

 

I would say addictive personalities best stay away, there's no moderating it... think an addictive person can have self-control or -restraint?  You'll likely be doing it before work again in no time.


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#18 knackers323

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Posted 02 October 2015 - 05:30 PM

Hi gamesguru what sort of driving signal did you have in mind when you said auto receptors may need to become unstuck?

Also as you sound very knowledgeable can you tell me why recreational drugs don't work on me like they do others and have you ever heard of it before and can I do anything about it.

Or is it likely to be genetic.

I get super paranoid and self conscious with weed and very critical of myself.

Ecstacy doesn't really work on me but it does give me a huge comedown for about a week. My mates get real high off a lot less and don't really get a comedown.

Coke works for me to some degree but rather than super confident and outgoing charged with energy I feel relaxed and just like to chill out but it also makes me self conscious.

What is going on here? Its like my brain is incapable of generating or using the same level of transmitters as other people.

Thanks for your help

#19 gamesguru

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Posted 02 October 2015 - 10:10 PM

Ecstacy doesn't really work on me
What is going on here? Its like my brain is incapable of generating or using the same level of transmitters as other people.

 

Precisely, my friend.  You are an alien, or mutant.  You also have eyes in the back of your head, and a second brain in your ballsack.

 

But have you tried LSD (not NBOMe) or alcohol :sleep: ?  Reckless doses?  Not all drugs act through the same neurotransmitters, so for them all to ineffective, you'd have to have polymorphisms on multiple neurotransmitter receptor types, which is exceedingly improbable (DNA fucks up here and there, but never everywhere, lest we prey to God).  This is probably why cannabis, cocaine and alcohol affect you (having major dopamine components), but MDMA and LSD won't (having major serotonin components).

I know SSRIs acutely block ecstasy by competing for access to SERT, and chronically block LSD/shrooms/NBOMe/DOB by downregulating 5-HT2A

My hypothesis therefore is a polymorphism (deformed protein structure) on SERT and/or 5-HT2A, which would be associated with things like depression, anxiety, ADD, certain personality disorders.

Maybe anxiety, given weed makes you unusually paranoid and introspective.

THC has this effect of inhibiting GABA release upregulated autoreceptors, and so I don't recommend it as a regular habit to friends with anxiety. ;)

 

Too many autoreceptors agonist

Too few autoreceptors    antagonist


Edited by gamesguru, 02 October 2015 - 10:17 PM.


#20 knackers323

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Posted 03 October 2015 - 03:44 AM

Hi mate thanks for your help. Sounds as if you know your stuff.

Xtc has worked in the past but it takes much bigger doses than what others need.

On the times it hasn't worked, do you know why I still get the comedown like the serotonin has been released?

I've tried shrooms and it was up there with the best 5 hours of my life.

Feel good when drink. Felt pretty good with baclofen, lamotrogine, aropax each.

I used to feel great with weed then the effects changed at about 15 year old.

Yes the cocaine does work but either not to the same degree or has a different effect on me to other people.it charges them up but does the opposite to me. Any idea why this would be?

When you were talking about the gaba auto receptors earlier in the thread you mentioned needing something to jolt them into action again. Like what?

I'm pretty sure I have some methylation issues that I should address but with my limited knowledge it sounds as though I'm low or have problems with in serotonin, dopamine, gaba. And possibly high in glutamate.

Fair assessment?

Yes your right, I've always had a tendency towards all those character traits associated with depression anxiety and over thinking and worry, thanks at least partly to the genes I've inherited.

Parents both have these, especially my Dad. I know I can't do anything about the genes but is there any thing I can do about epigenetics or medication and supplement s?

Sorry for all the questions. I really appreciate it. Thanks

#21 gamesguru

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Posted 03 October 2015 - 04:06 AM

Ginkgo, GABA(A) antagonist.

Ginseng, GABA(B) antagonist[2].

Bacopa boosts dopamine serotonin gaba, reduces glutamate norepinephrine.  Might be perfect for you.

 

At what age did you begin weed?  Weed is also serotonergic, but mostly dopaminergic.  It could be depression/anxiety causing around this age the 5-HT2A to become deformed (when did you become depressed), which could explain why this emerged, why weed stopped working at  age 15.

I wouldn't take large doses of MDMA brother, just to get an effect... just my 2 cents



#22 knackers323

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Posted 03 October 2015 - 04:41 AM

You don't happen to know a good brand?

Sorry I started smoking weed at about 15 and thought it was great about a year later it began to make me feel self conscious paranoid etc. So I stopped and I came back to pretty much how I was before I think.

I have always had a tendency to be self conscious, shy, introverted and Overthink and worry and be too serious, take things to heart and get down about things but I just felt with it. I could often see, even as a child that other people seemed happier than me.

I had felt little touches of what i later learned was depression many times growing up but I didn't get my first bout of depression until about a year or year and a half after stopping weed when after 6 or so months of heavy stress, I got a bout of bad stomach cramps that lead to prolonged and overwhelming fatigue.

Not sure how much the stress was responsible for this but I am starting to find that things that work on glutamate and gaba significantly reduce the fatigue, very quickly, even though I can't really see why this would affect fatigue to such a degree.

I have since learned that there is a theory that a problem with the gluta/gaba system my be involved in something called chronic fatigue syndrome
I don't take MDMA at all. Comedowns are too extreme

#23 sthira

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Posted 03 October 2015 - 05:09 AM

I have always had a tendency to be self conscious, shy, introverted and Overthink and worry and be too serious, take things to heart and get down about things but I just felt with it. I could often see, even as a child that other people seemed happier than me.

Gee, this could be explaining me, too. Shy, introverted, serious, dark, too smart, rarely happy, only brief encounters with joy, love, peace, even in the best of personal times -- all these personality traits have only deepened with age. Nothing has worked to brighten my mood consistently. Easy to give up. No drugs, no supplements, no therapy, no meditation, no hobbies or career dreams coming true, nothing works. My personality has stayed the same; but I'm becoming more eccentric as I get older. Meaning, I pretty much know nothing is going to transform my over-sensitivity to dark, serious aspects of everyday living. So I slowly have stopped caring. Fuck it. I wear clothes that are comfortable to me now -- hippie clothes, sandals or no shoes, my hair just kinda natty dreaded up into fat knots all on its own, and I don't care, but then, aww shit I do care now, of course, time to panic, I guess, over and over, on and on I face the panic of sudden self consciousness -- that's always there in waves coming and going, coming and going, in and out. Life is beautiful. Stuck inside my skin. Is anything worse than feeling constantly uncomfortable in your own body?

Some strains of weed worsen my mood, others lighten it. No noots ever worked as effectively as shrooms or indica. Nothing even comes close. I don't drink alcohol, not a drop because it just worsens the dark shade.

I had felt little touches of what i later learned was depression many times growing up but I didn't get my first bout of depression until about a year or year and a half after stopping weed when after 6 or so months of heavy stress, I got a bout of bad stomach cramps that lead to prolonged and overwhelming fatigue.

This part of your writing is also interesting to me. The onset of my depression also came on stronger with stomach cramps, and that later unexpectedly resulted in a ruptured appendix that nearly killed me at Marti Gras. Gut bacteria may have something to do with depression. Had your appendix checked out?

Edited by sthira, 03 October 2015 - 05:16 AM.


#24 gamesguru

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Posted 03 October 2015 - 03:02 PM

knackers, sounds like social anxiety, maybe generalized.  for anxiety try:    theanine/green tea, ginkgo, ginseng, ALCAR/PS, bacopa, kava, ash, valerian

for depression:   exercise and diet are useful, ^^^most of the above^^^, saffron, st john's, flax/fish, magnesium/chromium/lithium

chronic fatigue isn't well understood, i think a variety of factors contribute: genetics, viral load, poor diet, stress.

reminder:                                                                                                      Bacopa boosts dopamine serotonin gaba, reduces glutamate norepinephrine.  Might be perfect for you.

 

sthira, sounds like you are just depressed and intelligent, it tends to produce that sort of negative, pessimistic melancholia. also not caring about your appearance is a sign (of which i am also guilty: got mop hair, looong overdue for haircut).

 

 



#25 knackers323

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Posted 07 October 2015 - 09:48 AM

Sthira no haven't had my appendix checked, my stomach feels fine now. Yes I believe there is a lot of research right now pointing to the connection between the biodome and mental/physical health conditions. Yours sounds like depression to me also, maybe with dysthimia. At the moment I am taking lamotrigine and parnate and having decent success with it. I previously had good results with aropax but it killed my libido. It may not do the same to you. Keep trying things mate. The options out there are many. try something and let me know how you go

#26 Blackkzeus

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Posted 15 October 2015 - 09:53 PM

knackers, sounds like social anxiety, maybe generalized.  for anxiety try:    theanine/green tea, ginkgo, ginseng, ALCAR/PS, bacopa, kava, ash, valerian

for depression:   exercise and diet are useful, ^^^most of the above^^^, saffron, st john's, flax/fish, magnesium/chromium/lithium

chronic fatigue isn't well understood, i think a variety of factors contribute: genetics, viral load, poor diet, stress.

reminder:                                                                                                      Bacopa boosts dopamine serotonin gaba, reduces glutamate norepinephrine.  Might be perfect for you.

 

sthira, sounds like you are just depressed and intelligent, it tends to produce that sort of negative, pessimistic melancholia. also not caring about your appearance is a sign (of which i am also guilty: got mop hair, looong overdue for haircut).

 

Can you provide evidence that Bacopa reduces glutamate?



#27 gamesguru

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Posted 15 October 2015 - 10:14 PM

Low NMDAR levels and low binding indicate excessive glutamate release, low autoreceptor levels.

So Bacopa's reversal of this is probably achieved by lessening glutamate release

 

Decreased glutamate receptor binding and NMDA R1 gene expression in hippocampus of pilocarpine-induced epileptic rats: Neuroprotective role of Bacopa monnieri extract
The potential for antiepileptic drugs to negatively impact cognitive abilities has generated renewed interest in herbal drugs and formulations in the treatment of epilepsy. Bacopa monnieri is one such widely used revitalizing herb that purportedly strengthens nervous function and also possesses memory-enhancing, antioxidative, antiepileptic, and anti-inflammatory properties. We investigated the neuroprotective role of B. monnieri extract in alteration of glutamate receptor binding and gene expression of NMDA R1 in hippocampus of temporal lobe epileptic rats. In association with pilocarpine-induced epilepsy, there was significant downregulation of NMDA R1 gene expression and glutamate receptor binding without any change in its affinity. B. monnieri treatment of epileptic rats significantly reversed the expression of NMDA R1 and glutamate receptor binding alterations to near-control levels. Also, in the epileptic rats, we measured a significant increase in the activity of glutamate dehydrogenase, which neared the control level after B. monnieri treatment. The therapeutic effect of B. monnieri was also observed in the Morris water maze experiment. These data together indicate the neuroprotective role of B. monnieri extract in glutamate-mediated excitotoxicity during seizures and cognitive damage occurring in association with pilocarpine-induced epilepsy.

 


Edited by gamesguru, 15 October 2015 - 10:15 PM.

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#28 Flex

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Posted 22 October 2015 - 03:40 PM

This site has good common sense information on cannabis and brain:

http://norml.org/com...-a-user-s-guide

 

Information on it's neuroprotective properties:

http://www.ncbi.nlm....pubmed/10863546

 

,which is also patented by USA Gov:

https://www.google.c...tents/US6630507

 

Kind regards,

 

Looks quite to be an one-sided pro cannabis "just keep on smoking the Panacea" site

 

You never read about cognitive consequences of Cannabis in the Adolescence ?

 

The neural reorganisation during this time works, at least partly, via cannabinoid receptors.  Therefore is weed during this time not really good
 

Edit: There are also negative things for Adults, afaik pro-inflammatory effects via COX-2 activation, hippocampal apostosis via calcium overactivation (IIRC) & etc.

 

No offence but You see, its not that easy. Cannabis sites are as biased as the "wars on drugs" sites.


Edited by Flex, 22 October 2015 - 03:59 PM.

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#29 arska

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Posted 22 October 2015 - 04:04 PM

@Flex In my post I'm NOT recommending it for the Adolescence  nor anyone to consume.  The sites quoted in my post include also a reference to the pubmed site, which hardly promotes "just keep on smoking the Panacea". 

Another thing is that you do not need to smoke it and everything depends on amounts consumed ;-)

I have friends, who consume it for arthritis and they are perfectly fine with the calibrated doses. Could you pls post the link to "pro-inflammatory effects via COX-2 activation".

 

http://www.ncbi.nlm....m=cannabis cox2

 



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#30 gamesguru

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Posted 23 October 2015 - 06:42 PM

Δ9-THC-caused synaptic and memory impairments are mediated through COX-2 signaling.
Marijuana has been used for thousands of years as a treatment for medical conditions. However, untoward side effects limit its medical value. Here, we show that synaptic and cognitive impairments following repeated exposure to Δ(9)-tetrahydrocannabinol (Δ(9)-THC) are associated with the induction of cyclooxygenase-2 (COX-2), an inducible enzyme that converts arachidonic acid to prostanoids in the brain. COX-2 induction by Δ(9)-THC is mediated via CB1 receptor-coupled G protein βγ subunits. Pharmacological or genetic inhibition of COX-2 blocks downregulation and internalization of glutamate receptor subunits and alterations of the dendritic spine density of hippocampal neurons induced by repeated Δ(9)-THC exposures. Ablation of COX-2 also eliminates Δ(9)-THC-impaired hippocampal long-term synaptic plasticity, working, and fear memories. Importantly, the beneficial effects of decreasing β-amyloid plaques and neurodegeneration by Δ(9)-THC in Alzheimer's disease animals are retained in the presence of COX-2 inhibition. These results suggest that the applicability of medical marijuana would be broadened by concurrent inhibition of COX-2.

 

though a far cry from THC, non-decarboxylated CBD (CBDA) has the opposite effect:

Cannabidiolic Acid as a Selective Cyclooxygenase-2 Inhibitory Component in Cannabis
In the present study it was revealed that cannabidiolic acid (CBDA) selectively inhibited cyclooxygenase (COX)-2 activity with an IC50 value (50% inhibition concentration) around 2 μM, having 9-fold higher selectivity than COX-1 inhibition. In contrast, Δ9-tetrahydrocannabinolic acid (Δ9-THCA) was a much less potent inhibitor of COX-2 (IC50 > 100 μM). Nonsteroidal anti-inflammatory drugs containing a carboxyl group in their chemical structures such as salicylic acid are known to inhibit nonselectively both COX-1 and COX-2. CBDA and Δ9-THCA have a salicylic acid moiety in their structures. Thus, the structural requirements for the CBDA-mediated COX-2 inhibition were next studied. There is a structural difference between CBDA and Δ9-THCA; phenolic hydroxyl groups of CBDA are freed from the ring formation with the terpene moiety, although Δ9-THCA has dibenzopyran ring structure. It was assumed that the whole structure of CBDA is important for COX-2 selective inhibition because β-resorcylic acid itself did not inhibit COX-2 activity. Methylation of the carboxylic acid moiety of CBDA led to disappearance of COX-2 selectivity. Thus, it was suggested that the carboxylic acid moiety in CBDA is a key determinant for the inhibition. Furthermore, the crude extract of cannabis containing mainly CBDA was shown to have a selective inhibitory effect on COX-2. Taken together, these lines of evidence in this study suggest that naturally occurring CBDA in cannabis is a selective inhibitor for COX-2.

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