Please AVOID doing weed/cannabis/THC

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Meso
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Please AVOID doing weed/cannabis/THC

Unread post by Meso »

Hey guys/gals,

I'm bringing you something based on anecdotal reports of many patients that I've seen. It's a pattern that keeps repeating itself. That is, cannabis-induced crashes. Some people report getting a permanent crash after smoking weed while having PSSD. People who combined weed + SSRI also suffer from more severe PSSD symptoms overall.

Let me start by mentioning that weed has a post acute withdrawal syndrome (PAWS) of its own [1]. It occurs after someone does a massive dose of weed and they get stuck in depersonalization/derealization state for days, months, or even years. During adolescence, the cortical region is still not fully developed and it undergoes pruning. THC impairs this process and interferes negatively with GABA interneurons within the PFC and hippocampus. This leads to a higher risk of schizophrenia and an earlier onset among teenagers who smoke cannabis. This action of THC is mediated through CB1 receptors on the prefrontal cortex neurons (PFC), by blunting GABA interneurons expression (GAD67) [2].

This is also relevant to the adult matured brain. Weed's PAWS might be due to neurotoxic effects of high dose THC. Weed is generally neuroprotective, but it seems to follow an inverted U-shaped curve, with very low and very high doses being neurotoxic due to triggering neural apoptosis. They also facilitate long-term depression (LTD) of cortical and hippocampal neural circuits [3][4][5].

You might be wondering, how is that relevant to PSSD?
SSRIs modulates endocannabinoid levels across the brain in a positive manner[6]. Fluoxetine, and maybe other SSRIs, upregulates CB1 receptors in the PFC and this effect remains even after 10 days of withdrawal [7]. Antidepressants can modulate the eCB system across many brain regions [8]

1: High dose THC is needed to trigger weed PAWS that can last for years.
2: SSRIs and other classes of antidepressants potentiate the endocannabinoid system both directly and indirectly.

From these 2 points, SSRI can alter people's response to THC due to heavy modulation of eCB system and it might even potentiate it enough to trigger a weed PAWS using commonly abused doses.

This might crash some people but some others could be totally okay mixing both. It comes down to genetic vulnerability.
It's not worth the risk, imo.
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fth
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Re: Please AVOID doing weed/cannabis/THC

Unread post by fth »

Hi! I did my best to understand this post but I wanted to make sure I got it right. So you're basically saying that mixing SSRI's and weed could lead to weed PAWS, and that people who mixed SSRI's and weed tend to have worse PSSD symptoms than those who didn't mix?

If that's true, would there be a need for me to quit now anyway? I quit SSRI's in July 2019 and I still smoke weed (combined the two before quitting as well). If quitting could do anything for my PSSD then I'd happily drop weed. Basically: does this still matter for those who aren't on SSRI's anymore, or is it just the mixing that's not a good idea?

Apologies for possible incorrect English.
► Fluoxetine & methylphenidate (03/2016 - 07/2019)
► Symptoms started somewhere in 2018
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SueDenim
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Re: Please AVOID doing weed/cannabis/THC

Unread post by SueDenim »

Hi, can you please elaborate on 'some people report getting a permanent crash after smoking weed while having PSSD'?

Do you mean to say that people who have PSSD and who smoked weed cannot get better? I have smoked a lot of weed in my late teens and early 20s, nearly every day for years all while taking a very high dose of sertraline and then going cold turkey. After I quit SSRIs I continued to smoke weed heavily on a daily basis for years after. Stupid, I know.
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succubus76
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Re: Please AVOID doing weed/cannabis/THC

Unread post by succubus76 »

I got dp from weed luckily only lasted 2 days.
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Delfador
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Re: Please AVOID doing weed/cannabis/THC

Unread post by Delfador »

I agree, in the past, weed gave me periods of pssd-like episodes before I got the real big pssd.

Plus, it's worth noting that CBD is a 5ht1a agonist, which might desensitize receptors more
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Joao Paulo Brasil
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Re: Please AVOID doing weed/cannabis/THC

Unread post by Joao Paulo Brasil »

Olá, sou o João Paulo e tive depressão em 2019, comecei a tomar escitalopram por dois meses, depois mudei para Venlafaxina e tomei por mais 7 meses. Comecei com uma dosagem de 37,5 mg, depois 75 mg, depois 150 mg e até a dosagem máxima de 225 mg. Quando cheguei à dosagem máxima comecei a me sentir muito mal, estava com muita insônia, falta de emoção e então resolvi parar o tratamento, parei imediatamente. Após interromper o tratamento fiquei 30 dias com extrema ansiedade, por isso decidi começar a tomar escilatopram 10mg, e consegui aliviar os efeitos da ansiedade. Durante parte do tratamento com venlafaxina, também tomei um medicamento para durmi, chamado Zolpiden.

Já fazia quase um ano que tomava antidepressivos e poucas vezes me sentia curado, só me traziam grandes problemas. Eu estava realmente cansado de tomar essas drogas, então parei de tomá-las. Comecei a fumar maconha todos os dias antes de dormir e com duas semanas estava indo muito bem, estava muito feliz, não conseguia acreditar que minha depressão e ansiedade estavam passando. Por isso, fumei todos os dias durante 3 meses.

Durante o tratamento com antidepressivos tive problemas sexuais, como baixa libido, dormência peniana e demora para ejacular, e quando comecei a fumar maconha minha libido e minhas ereções começaram a diminuir, chegou ao ponto de simplesmente desaparecer. Então parei de fumar ...

Hoje, dois meses depois, estou totalmente sem libido, sem ereções pela manhã, orgasmos muito fracos. Não tenho dormência genital e posso deixar meu pênis duro normalmente. Minha depressão e ansiedade foram curadas pela maconha.

Você acha que a maconha pode ter causado PSSD ou contribuído para isso?

Meu psiquiatra me deu bupropiona para recuperar minha libido, mas tomei por duas semanas e comecei a ter insônia, ansiedade e muita tensão, então parei de tomar.
Escitalopram and venlafaxine (7 months)
With PSSD FOR MORE THAN 3 YEARS.
bockemossen
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Re: Please AVOID doing weed/cannabis/THC

Unread post by bockemossen »

Hello Meso

I read you say that lithium could potentially reverse epigenetic changes done by weed. Could this be changes done 10 years ago in late adolescence like social and cognitive impairment and social anhedonia?
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Meso
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Re: Please AVOID doing weed/cannabis/THC

Unread post by Meso »

fth wrote: Sat Nov 14, 2020 12:22 pm Hi! I did my best to understand this post but I wanted to make sure I got it right. So you're basically saying that mixing SSRI's and weed could lead to weed PAWS, and that people who mixed SSRI's and weed tend to have worse PSSD symptoms than those who didn't mix?
Mixing weed and SSRI can lead to profound PSSD that's typically more severe with depression, anhedonia, and dp/dr. Although we can't make a statistically sound argument given the low overall number of PSSD patients, I've already seen ~6 people who crashed miserably when combining weed and SSRIs. That's good enough for me to voice a warning.
fth wrote: Sat Nov 14, 2020 12:22 pmIf that's true, would there be a need for me to quit now anyway? I quit SSRI's in July 2019 and I still smoke weed (combined the two before quitting as well). If quitting could do anything for my PSSD then I'd happily drop weed. Basically: does this still matter for those who aren't on SSRI's anymore, or is it just the mixing that's not a good idea?

Apologies for possible incorrect English.
Smoking weed has worsened a member on my server permanently despite not being on SSRIs anymore. He quit weed but that didn't matter much after the fact. It comes down to luck and genetics, I reckon.
SueDenim wrote: Sat Nov 14, 2020 1:20 pm Hi, can you please elaborate on 'some people report getting a permanent crash after smoking weed while having PSSD'?

Do you mean to say that people who have PSSD and who smoked weed cannot get better? I have smoked a lot of weed in my late teens and early 20s, nearly every day for years all while taking a very high dose of sertraline and then going cold turkey. After I quit SSRIs I continued to smoke weed heavily on a daily basis for years after. Stupid, I know.
I know 6 people who crashed severely after smoking weed on several occasions. I don't know if smoking weed would slow down recovery from PSSD, but it can certainly crash you further.
succubus76 wrote: Sun Nov 15, 2020 3:52 am I got dp from weed luckily only lasted 2 days.
You are lucky. I know person who never recovered from dr/dp and got worse PSSD. Another person recovered from a cannabis+SSRI crash but it took him 1 year of being drug free.
bockemossen wrote: Mon Jan 18, 2021 5:35 pm Hello Meso

I read you say that lithium could potentially reverse epigenetic changes done by weed. Could this be changes done 10 years ago in late adolescence like social and cognitive impairment and social anhedonia?
Lithium is a HDAC inhibitor that upregulates ER signaling. This leads to upregulation of TET1 which is an active demethylating enzyme (i.e. works for neurons as well). On paper, it's good enough to reverse epigenetic changes when dosed right. A few of the people I recommended lithium to managed to recover from some sexual symptoms of PSSD. But it's all theoretical / trial-and-error.

I don't know if lithium can reverse neuronal changes of weed, especially adolescence use of weed, because weed during adolescence profoundly changes the structure of the PFC (neuronal pruning). It might help a weed induced crash, again: theoretically. It requires trial and error.
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Sb919
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Re: Please AVOID doing weed/cannabis/THC

Unread post by Sb919 »

Cannabis seemed to be the only thing that has helped me so far. It didn't fully bring me back or anything even close, but I was well enough to keep me away from being on the forums all the time for a year+. (this thread didn't exist at that time)

I quit again in the beginning of February due to anxiety over my relationship, and crashed similarly to when I first discontinued SSRI's 3 years ago, although not exactly the same. No interest in anything, premature ejaculation back full force, zero sex drive, depression/rumination, sleep disturbances, massive brain fog, weak/no morning wood... back to refreshing the forums every 10 seconds etc... and now even when I try to smoke again, it just makes me feel numb and slow, and still unable to focus on anything (unlike up to a few months back, it was doing the opposite). It is not working anymore for me since I stopped, and now I seem to be stuck like this.

Any ideas on what it is that I may have been having a positive response to, or what has happened? Dopamine maybe? Or 5ht1a agonism? Maybe I was still in PAWS from quitting years prior when I first discontinued SSRI's?

Could use any suggestions on what to try from here if possible, if you have the time.
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Meso
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Re: Please AVOID doing weed/cannabis/THC

Unread post by Meso »

Sb919 wrote: Mon Mar 15, 2021 9:25 pm Any ideas on what it is that I may have been having a positive response to, or what has happened? Dopamine maybe? Or 5ht1a agonism? Maybe I was still in PAWS from quitting years prior when I first discontinued SSRI's?

Could use any suggestions on what to try from here if possible, if you have the time.
I don't know how THC PAWS is mediated. If it's receptor desensitization, then maybe CBD/CBG can help since they are weak eCB receptors antagonists. Also, generally speaking, people who suffer from depersonalization/derealization use Naltrexone to try and cure these symptoms. I don't know how much this is effective.
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