Cannabigerol/CBG For PSSD/Libido (5-HT1A Modulatio)

Lokzo

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I wanted to write this post to hopefully HELP others out there with sexual dysfunction symptoms associated with PSSD.


Today I want to discuss my (5+ year long journey researching & experimenting) findings.


A little background:
As many of you already know, I am the guy (Amongst many others) who got "cured" by cyproheptadine usage.


But what "cure" am I referring to???


Well, specifically, POST-SSRI-Sexual Dysfunction symptoms (PSSD).


I contracted PSSD from Ashwagandha usage, amongst many other dudes unfortunately.



You can read my viral article here:

https://medium.com/@LucasAoun/ashwagandha-can-cause-anhedonia-pssd-blunted-emotions-and-apathy-97fb99855f28


But it doesn't work when we dose it ACUTELY.



In fact, a single dose of cyproheptadine (<1mg), will cause the following effects:

-Horrible libido (Normal erections).
-Zero orgasm feeling.
-No climax.

-Fatigue.

-Ravenous appetite.

-Incredible digestion.

-Numbing of all my emotions.



BUT...... It's the REBOUND of cypro.... That CURES me of PSSD.


DAY 4 and 5 AFTER using 1mg of cypro, there's this incredible SNAPBACK effect....


Orgasm returns, no more blunted libido, everything amazing, all emotions online.


But WHY....

What is happening 4 days after Cypro?


My current theories are as follows:

2. 5-HT1A receptor modulation/upregulation from hardcore antagonism?


Other compounds that have “given me windows” of cure are:
1. St John’s Wort (You can read my post here - St. John's Wort: PSSD Eliminated, Anhedonia Gone, Emotions Online!)

2. Zeolite.

3. ALCAR (Only lasts a day or two, then WORSENING of symptoms).

4. Homeopathic Phosphorus (Don’t even fkn ask me how this works, and also, don’t call it a placebo, because I have gotten my brother to BLIND FOLD me and test it out on me).


So now we enter CBG Extract:

The reason why I decided to try CBG extract was based on ONE finding:

“Evidence that the plant cannabinoid cannabigerol is a highly potent α2-adrenoceptor agonist and moderately potent 5HT1A receptor antagonist”
(
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2823359/)


This caught my attention because as you know, Cyproheptadine is ALSO a 5-HT1A antagonist!!


Now here’s where it gets super interesting:

When I acutely dose CBG orally (Between 10-40mg), I remember the first day I tried it, feeling heightened energy and stimulation. I was generally in a good mood.

But that’s NOT what I was looking for.

Remember, the whole goal here is to alleviate my messed up 5-HT1A signalling that causes PSSD-like symptoms.

That night after dosing, I slept very average, and for the first time in years I woke up at like 3-4am HUNGY!!!

I rarely wake up hungry like that.

This effect has continued.

So after continuous dosing, I quickly noticed something rather spectacular.

My PSSD symptoms disappear about 10-12 hours after dosing CBD… As in, when it “wears off” I feel my orgasm return full strength and penis to brain connection return again.

So now I am trying to dertermine whether or not I can use CBG as a form of “re-set” instead of Cyproheptadine to help my condition.

So far so good, and only time will tell how long this rebound lasts.



Some other effects about CBG:
CBG can activate alpha α2 adrenergic receptors and block CB1 receptors (Cascio et al., 2010), suggesting CBG does have therapeutic potential in the treatment of depression.
 

Lokzo

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CBG Extract notes:

Orexigenic role of CBG













Anecdotes:

“CGB doesn’t make me feel like that at all, and gives me a steady stream of concentration (similar to coffee but without the shakes and anxiety)”

“IMO CBG has a bit of a stimulant effect for me which could trigger some of those anxious feelings”


“After taking CBG w/coffee, I found that I get a super energy boost after about 20 minutes and a general good vibe that lasts almost 4-5 hours. I do not get rapid heartbeat like when I have too much caffeine, so that's cool. I did not have trouble sleeping the few times I took .5ml more in the evening, and seemed to still get an energy boost from it.”

“TLDR: cbg/cbd mix gives me good clear-headed energy + good vibe without anxiety or that too much coffee feeling.”


“Just take like one hit and see how you feel. I have experienced a buzz from cbg but it's not exactly like thc.”


“High doses(50+mg) of CBG isolate taken sublingually gives me a coffee-like buzz with a mild THC-like body buzz. My favorite way to use CBG is to take a decent sized sublingual dose and then take a big bong rip of a strong sativa. Really enhances the heady effects of THC without adding more anxiety.”


“I get pretty strong energizing effects that last 4-5 hours when I take a big sublingual dose. It's like really strong coffee minus the jitters.”


“I get that. I take it orally in the morning and get a solid buzz for 4-6 hours. It makes me focused, clear-headed, and greatly reduced my anxiety during that time. It's basically like coffee perfected imo”

CBG appears to act as an agonist at the alpha-2 receptor (with varying EC50 values reported) and all of the TRP family channels (except TRPM8, at which it is reported to act as an antagonist). Together, these data suggest that the physiologic effects of CBG tend towards Gi-mediated inhibition, autoregulatory activity, and calcium-based signaling both by ion channels and PKC




"CBG is actually an alpha2-adrenoceptor agonist, which means it activates your adrenal receptors (the same receptors adrenaline etc. activate).


CBG also antagonizes CB1 receptors, which is the exact opposite of what THC does at that receptor. So it could simultaneously be reversing possible over-activation and subsequent lack of motivation caused by excess consumption of THC.




“CBG seems to be a fairly potent anxiolytic. Promotes some wakefulness, focus, and sociability as well. I've found that something like a 3:2:1 mix of CBG:D8:CBD seems to be the most effective so far.”



“In my case cbg.is an uplifter. Def not a night medicine . It relax you but gives you energy”


“I was recently diagnosed with anxiety disorder and can’t smoke THC anymore:( However, I’m using CBG by itself to replace THC and holy hell is it working! Not the same high, but definitely a buzz. Anxiety melts away quickly. I love it”


Alpha 2-adrenoceptor agonists stimulate growth hormone secretion but have no acute effects on plasma cortisol under basal conditions


It's been a few weeks that I started vaping CBG flower (often mixed with CBD flower, sometimes a little regular bud too). I like the effects this far, very clear headed indeed. However I often feel some mild body high the next day, usually in morning and late afternoon.



“CBG in higher doses (60-75mg+) gives me sedation, low doses (10-30mg) energy/focus”

In my experience it's more on the energizing side.

“I tend to take it in the morning (seems to energize me), and while my head is completely clear I feel uplifted and more talkative/less negative throughout the day.”

“Yea, I often add CBG in the mornings or before going in public, gives a little social warmth where I don't feel as exposed.”

“It gives me a feeling similar to the initial rush of a sativa high. I got distillate from IHF (it’s str8 rocks/hard crumble consistency) and have been vaping it out of my grasshopper also in the morning. I’m a fan it’s a nice buzz for daytime use.”

“I've been taking CBG regularly for a couple of months now. I like it and agree that there's a subtle energizing effect.”

"Cbg 50mg with cbd 50mg is amazing feels like weed but without the high.



Its alot more mood uplifting and relaxing than weed and just cbd by its self



"With CBG I found I do need to take a larger dose compared to CBD. I've been sourcing my CBG from flowerchildcbd - I get their 1400mg CBG tincture which is fairly expensive at $130, but works really well for me and I like that it is a high quality full plant extract (ethanol extraction). I take a single sublingual 30mg to 50mg dose in the morning. I find it very relaxing and improves my mood and motivation throughout the day. I have not noticed any increase in appetite. Often I will mix in a little bit of CBD tincture , usually 5-15mg to my morning dose as this seems to potentiate the effects and provide a better balance of relaxation vs. stimulation. Note that my experience seems to be the opposite of most people where they find CBD provides relaxation and CBG stimulation, so YMMV. I have tried vaporizing CBG flower and do find that more stimulating/energizing compared to the tincture, though that could be due to the specific CBG strain profile.”



“80mg CBD, 20mg CBG, sublingual and then swallowed... that's how I started my day and how I start most days. The addition of CBG to my tincture regimen has been huge in terms of positive mood and motivation. High doses of CBG get really cool as well... slightly psychedelic. I'm a big fan. For whatever reason I get more out of ingesting CBG than smoking CBG flower.”


“A recent study confirmed that CBG is a CB2 receptor partial agonist with minimal effects on the CB1 receptor. This CB2 mechanism can explain many of the anti-inflammatory effects that have been reported:

Keep in mind that this is not a unique activity. Several other phytocannabinoids and synthetic cannabinoids can activate the CB2 receptor. Plus you also have the cannabis terpene β-caryophyllene, which is a full CB2 agonist.



CBG Is A Serotonin 5-HT1A Antagonist

People talk about the entourage effect like it is always a good thing, but that is not really the case here. CBG is a moderately potent antagonist of the 5-HT1A receptor. It was able to block the anti-nausea effects of CBD. This probably also extends to anything mediated by 5-HT1A, including both the anti-nausea and anti-anxiety effects of CBD and CBDA.

However, 5-HT1A antagonists may also have some therapeutic properties. Studies suggest that overactive presynpatic 5-HT1A receptors can reduce prefrontal serotonin release and inhibit the effects of antidepressants. Therefore, inhibition of 5-HT1A receptors has been proposed as a strategy to accelerate the effects of antidepressants.

Although CBG did not have an antidepressant effect in mice after a single dose, an effect may be seen with multiple doses or when given in combination with SSRIs.



•CBG could inhibit COX-2 activity, but only with very low potency

•CBG reduced bladder contractility (not through CB1 or CB2).

CBG could activate TRPA1, TRPV1, and TRPV2

•CBG was a TRPM8 antagonist.

•CBG could inhibit GABA reuptake, but it is not clear this occurs in vivo since CBG did not affect anxiety behaviors in mice.

•CBG could inhibit growth of various cancer cell lines, including colon (through TRPM8 inhibition), oral cancer, breast, prostate, and stomach.



The most obvious direction for more research would be pain. This is the most commonly cited condition for using CBG and CBG has activity in models of visceral pain and neuropathic pain (according to data in the GW Pharma patent).
 

CalmAmygdala

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Have you reversed the damage done to your 5HT1A system from ashwagandha yet? Sounds like you've been diligently combatting it for a while. I'd think by now you'd achieved some long term upreguation/sensitization to that receptor system and could sit back and coast for a while
 

Lokzo

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Have you reversed the damage done to your 5HT1A system from ashwagandha yet? Sounds like you've been diligently combatting it for a while. I'd think by now you'd achieved some long term upreguation/sensitization to that receptor system and could sit back and coast for a while

I definitely have induced LONG lasting windows, and for sure have seen (well not literally lol) positive changes to my 5-HT1A system.

Unfortunately there are many things that can HURT me though:
-Tapioca Starch.
-Potatoe Starch
-Ginger.
-Zinc
-Magnesium
-Spinach.

I seem to still be super sensitive to all those + many more.

For eg. Potatoe starch can cause numbness for up to a whole week.
 

CalmAmygdala

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Have you tried running a moderate dose of cypro (4 mg) for a good thirty day stretch, or a moderate dose of metergoline 2.5 plus for the same length of time? I'd think that might achieve some long term 5ht1a sensitivity
 

Lokzo

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Have you tried running a moderate dose of cypro (4 mg) for a good thirty day stretch, or a moderate dose of metergoline 2.5 plus for the same length of time? I'd think that might achieve some long term 5ht1a sensitivity

I might do this if I need ULTRA Slowing down... Like if I know I need to rest and recover, no training for like a whole week (which is never lol).

But mega doses of cypro like that I know would work wonders, its just that I know it will hurt me for a whole week... Maybe after new years I might do this.

Actually I always said that before a music festival, I would have 4mg of Cypro on the monday night to feel AMAZING the Friday night (when the cypro rebounds).
 

CalmAmygdala

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Yeah. Short term sacrifice for long term gain would be the mentality. I've been perusing your website, I see you advocate dihexa usage. Have you used it personally and if so, through what method of adminstratrion? I've read that oral has poor bioavailability. What are your favorite nootropics?
 

Lokzo

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Yeah. Short term sacrifice for long term gain would be the mentality. I've been perusing your website, I see you advocate dihexa usage. Have you used it personally and if so, through what method of adminstratrion? I've read that oral has poor bioavailability. What are your favorite nootropics?


Yeah, the whole premise of "Get bad to get good", I have explored that topic a lot!

Yeah DIHEXA is unique, haven't actually tried it yet. I have close nerd friends who have and say it can acutely increase anxiety, but then it reduced their sleep requirements, and improved mood.

Funny you ask, I am just about to launch a Nootropics Course...It's entirely built, just have to release it with my marketing team.

It's here btw (please don't share to anyone yet):
https://optimal-health-masterclass-series.teachable.com/p/biohacking-your-brain-nootropics-cosmetic-neurology-masterclass/
 

CalmAmygdala

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Yeah I ran it once a couple years ago. I did 20 mg oral every day for 7 days in a row! It makes sense to dose it weekly though. Never considered that. I experienced some anxiety but no definitive improvements in cognition that I could pinpoint, unlike cerebrolysin, 9mbc, or other powerful neurogenics. I'll check the course out
 

CalmAmygdala

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Of Dihexa.

But regarding cypro, Ive been running 4 mg a night for 30 days now. Some days I would titrate to 1 mg (while stacking with 1-2.5 mg metergoline). I think I'm going to stop tonight though and see how I feel the next few days
 

Lokzo

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Of Dihexa.

But regarding cypro, Ive been running 4 mg a night for 30 days now. Some days I would titrate to 1 mg (while stacking with 1-2.5 mg metergoline). I think I'm going to stop tonight though and see how I feel the next few days


What are your main symptoms or areas you're trying to enhance?
 

CalmAmygdala

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It started off as a quest to reverse the damage done by a year or more of ashwagandha usage, but its turned into a quest to get my brain chemistry to exist in the "sweet spot." What Hans refers to as the ?"high dopamine personality." His articles, along with Haidut's supplements, have been nothing short of life-changing for me. After a couple weeks of cypro/meter, I felt changes taking place in my perception of reality and social interactions with people....improvements. I am an INTP on the myers briggs and have been borderline autistic the majority of my life.... cypro/meter have seemed to reverse this... completely it seems. Other supps have help me make significant improvements, most noticeably uridine, 9mbc, cerebrolysin, and 7,8 DHF. And Semax. But none of this have been quite as profound as cypro/meter. I think I had a severely ****88 up serotonin system from birth, exacerbated byt drug usage throughout my late teens and 20s, especially a particularly horrifying experience where i took way too much LSD and had a terrifying trip for 12 hours.

I am my own worst enemy. To complicate everything, I recently started running Test Cyp at 600 mg weekly to try and get some gains (I'm on TRT normally), and its been a b**** trying to get my AI dosage right. What initially motivated me to try it was the addition of androsterone to my supplemental arsenal. I was running it on my TRT dose of test and finding it had no sides other than sedation, However, I quickly found out that it is not near strong enough to contro9l estrogen on supraphysiological dosages of testosterone (I dont even think it was controlling it on my TRT dose) so i've had to switch back to exemestane. Anyways, my libido is ****88 right now but i cant tell if its the high/low estro or something else (the cypro).

Thats why I'm going to drop the cypro tomorrow, to see if my libido comes back online (your post about cypro interfering with your libido caught my eye - I had assumed that the low serotonin state brought about by cypro would increase libido).
 

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