Mechanisms behind cannabis hallucinations and dysphoria and how to tackle them

[Neuroprotection]

i’ve never tried any form of cannabis in my life, but I know that most people use it for its mind altering effects which include relaxation, altered consciousness including hallucinations/Thought patterns and mild memory impairment.
On the other hand, I’ve heard that many people hate weed and have tried unsuccessfully for many years to acquire a taste for it. these people complain of dysphoria and paranoia along with forgetfulness and the same goes for people receiving medical cannabis as a treatment for trauma.

Interestingly, it has been discovered that THC and other psychoactive cannabinoids don’t just rely on the CB1 receptor to produce their effects. in fact, they cause this receptor to form complex’s called Heteromers with other unrelated receptors, the most notable being with the 5HT2A. yes, that’s the psychedelic receptor where magic mushrooms and LSD produce their classical effects. in animal studies, blockade of 5HT2A receptors prevents memory impairment and social behaviour alterations produced by THC, whilst leaving the analgesic and temperature lowering effects intact. this has important therapeutic implications for humans Who may want the analgesic and Neuroprotective effects of THC without The powerful psychoactive effects. personally, I would be interested in trying such a combination both for religious and personal reasons.
As for THC induced dysphoria, I assume blocking the 5HT2A receptor could address that, but perhaps you desire some of the psychoactive effects minus the paranoia and dysphoria. well, this is where blocking the kappa opioid receptor might help. apparently, THC stimulates the production of large amounts of Dynnorphin, An opioid peptide responsible for inducing despair, depression and under some circumstances, possibly psychosis like behaviour. it is the complete opposite of endorphins and a bit worse, and its target is the kappa Opioid receptor. on a sidenote, that’s the same Receptor at which salvia divinorum/Salvinorin A acts and it’s the most potent natural hallucinogen known. animal studies show that coadministration of THC with a kappa opioid antagonists prevents THC induced aversion and instead, unmasks a rewarding effect/Conditioned place preference.

As I am blind, it takes me time to post links and I must do them on another post, but in the meantime, does anyone have any thoughts on what I’ve said so far?

 

[Darksidesam]

something to consider here is that very commonly (Im not telling anyone to take ecstasy to consume cannabis under any circumstances by the way) lots of people enjoy the cannabis high in particular after using ecstasy on the comedown of it. For some reason it seems to do what you describe and block the potential negative effects and i must confirm from personal experience that i have had crystal clear highs when i have used cannabis on an ecstasy comedown. It also plays down to personality type if you are naturally over analytical, self-critical or get 'stuck on a loop' of negative thoughts then cannabis can may well have this effect on such an individual who chooses to consume it.
This is where doseage comes into play massively, as if the person has little to no tolerance and consumes a large amount (commonly seen with edibles and dabs even vape pens) they risk getting stuck into that loop for a long time, where as i find for example vaping dry herb sensibly ( just 1 hit or 2 hits pacing yourself and conserving your herb) its less likely to happen and if it does you can be glad to know you will only experience these effects for a short duration (approx < 2 Hours)
You state that you are blind, well this is a very interesting topic in that you are briefly describing psychosis (hallucinating on weed is not really an ideal effect) and weed psychosis is constantly compared to psychosis and schizophrenia. Well, according to research people who are born blind are seemingly resistant to schizophrenia for some reason and i wonder this information could be used further with cannabis and psychosis studies.

 

[PtahTek]

Not sure what to say without the actual studies on this but am amazed that one person can be quite chill and another just the opposite on the same bud of weed.
Goes for most substances it seems. No one size fits all kinda thing.
I have felt all of the above effects posted at some point in my use of MJ... even the hallucination (which may need to be defined a little maybe). Seeings things that arent there? Who is to say it is not difinitively? We do not know that which we do not know. We can only sense about 10% of our surroundings it has been said. IDK
If hallucination entails seeing a situation from a different perspective or the like then yep IME it is hallucinogenic.

 

[Egzoset]

Salutations Neuroprotection,

...I am blind...

To me that's the most stimulating aspect in your post, as i've myself focussed on friendlier vaporization systems with no displays, nor even buttons. Most unfortunately manufacturers have an obvious habit to address THEIR own needs in priority; their designs rarely begin with the task to perform, which is to simply remove all vilification factors, ideally...

In my lamentable canuck counrty i believe the Volcano has even been certified by Health-Canada, which is a sinister farce considering the ritual refocusses a consumer's own universe around paraphernalia for long minutes waiting for a balloon to fill up, wasting some 300 grams or more only to generate fair aroma/taste appreciation. This may seem appropriate for intense "medical" missions but i get a definite impression it's nothing but fame base on its price-tag and the taxes comming with it. The Syqe promissed much more rational dosing nearly a decade ago in comparison.

As for the rest mind never been as sharp as after i discovered vaporization, which put an end to some long abstainance period following a hashich smoker carreer, actually.

The term hallucinations sounds more like stigmatization to me, but i did use to enjoy a rare physical manifestation of apprehension from just smelling condensed rosin, e.g. before the actual intake... I sort of miss it today although other gains were put in the balance.

Cannabis emancipation ain't too different from other skills acquired via trial & error, like mastering music or biking, etc. This implies that society's bigot prohibitionnists are mis-guided pushing abusive interference as it merely serves to interrupt a natural process with no health-wise alternatives, worse: the bigots contribute with plenty of *VILIFICATION* vectors starting with failing to fix the broken consumption method democratized by the 1881 patent of James Albert Bonsack, a roling machine...

To top it all almost 10 years past the UN's FCTC/COP6 of late 2014 nobody talks about consumption tools and their associated ritual - but that's Norml since it was conceived in absence of journalists/observators and performed behind close doors in Moscow/Russia anyway!

In addition beware as there's plenty of "disphoria" simply watching Star Trek promoting alcohol day & night on cable TV while demonizing "drugs" in such a ridicule manner best explained by Earl Blumenauer addressing Michael Botticelli in USA: how do we expect kids to listen seriously at adults in panick in front of ¢amera$ (posing as references on marihuana)! Moreover, if we dig further into scientology/religion based treatment, euh... Well, the trauma level possibly
including endoctrination-induced suicide, try these keywords on Google for example:

"Fix-my-Kid"
"Kids-for-Cash"
"Narconon Trois-Rivières"

Oddly enough mass-media won't tell about those little details if it can avoid it and flood the mediatic environment with cannabis candy "poisoning" every halloween, if not all year long.

In The Name Of Children.

 

[Mjäll]

A source would be good for the receptor heteromerization. It's news to me.

Kratom may be a 5HT2A antagonist and it makes me very tolerant to the psychoactive effects of THC. When i'm on kratom i can't get enough weed, and i always retain a sense of sobriety. I have even pushed it toward a cannabinoid overdose in the somatic department without getting enough, so to speak. The combination is rather enjoyable but not at all synergistic. Maybe kratom could let people with strong boundaries explore cannabis without some of the freakier effects. Personally i just love the freakiness and have never felt any analgesic or otherwise overtly "medical" effects from cannabis. To me the healing power is inseparable from the psychoactivity.

 

[Nas47]

never had any visions from cana.just relax,munchees possible,enhanced feeling of rhytm,music...etc.....even analgesia in light form.nothin simmilar to psychedelics.its in separate category of substances for me....quite unique even-plant cannabis-buds&resin......as for religious purpose-rastafarians use it,some coptic denominations too.

 

[Kaleida]

Here is the link to the study about cannabis acting through CB1-5-HT2A receptor heterodimers, I've seen it many times.

Cognitive Impairment Induced by Delta9-tetrahydrocannabinol Occurs through Heteromers between Cannabinoid CB1 and Serotonin 5-HT2A Receptors

Specific subtypes of cannabinoid and serotonin receptors interact to form heterodimers that mediate the cognitive deficits—but not the analgesic effects—induced by tetrahydrocannabinol, the major psychoactive constituent in Cannabis sativa.

journals.plos.org

i’ve never tried any form of cannabis in my life, but I know that most people use it for its mind altering effects which include relaxation, altered consciousness including hallucinations/Thought patterns and mild memory impairment.
On the other hand, I’ve heard that many people hate weed and have tried unsuccessfully for many years to acquire a taste for it. these people complain of dysphoria and paranoia along with forgetfulness and the same goes for people receiving medical cannabis as a treatment for trauma.

Interestingly, it has been discovered that THC and other psychoactive cannabinoids don’t just rely on the CB1 receptor to produce their effects. in fact, they cause this receptor to form complex’s called Heteromers with other unrelated receptors, the most notable being with the 5HT2A. yes, that’s the psychedelic receptor where magic mushrooms and LSD produce their classical effects. in animal studies, blockade of 5HT2A receptors prevents memory impairment and social behaviour alterations produced by THC, whilst leaving the analgesic and temperature lowering effects intact. this has important therapeutic implications for humans Who may want the analgesic and Neuroprotective effects of THC without The powerful psychoactive effects. personally, I would be interested in trying such a combination both for religious and personal reasons.
As for THC induced dysphoria, I assume blocking the 5HT2A receptor could address that, but perhaps you desire some of the psychoactive effects minus the paranoia and dysphoria. well, this is where blocking the kappa opioid receptor might help. apparently, THC stimulates the production of large amounts of Dynnorphin, An opioid peptide responsible for inducing despair, depression and under some circumstances, possibly psychosis like behaviour. it is the complete opposite of endorphins and a bit worse, and its target is the kappa Opioid receptor. on a sidenote, that’s the same Receptor at which salvia divinorum/Salvinorin A acts and it’s the most potent natural hallucinogen known. animal studies show that coadministration of THC with a kappa opioid antagonists prevents THC induced aversion and instead, unmasks a rewarding effect/Conditioned place preference.

As I am blind, it takes me time to post links and I must do them on another post, but in the meantime, does anyone have any thoughts on what I’ve said so far?

There's logic to what you've proposed, although the first thing I have to ask is, have you considered using something like ∆8-THC instead? There are many people who specifically praise it for being an alternative to ∆9-THC with a less intense head trip and fewer dysphoric feelings. I haven't really kept up with the recent development of legal THC alternatives lately but I know there are many other options like it too. I have used ∆8-THC personally and definitely did find it lighter than ∆9-THC while still being similar, although reactions do vary from person to person as with any drug.

I ask mainly because getting something like ∆8-THC is going to be a lot easier than getting a selective 5-HT2A receptor antagonist and a selective kappa-opioid receptor antagonist to mix with your cannabis, and require less use of experimental drugs in the process.

something to consider here is that very commonly (Im not telling anyone to take ecstasy to consume cannabis under any circumstances by the way) lots of people enjoy the cannabis high in particular after using ecstasy on the comedown of it. For some reason it seems to do what you describe and block the potential negative effects and i must confirm from personal experience that i have had crystal clear highs when i have used cannabis on an ecstasy comedown.

This is completely true, and it also gives you iron lungs. Smoking cannabis on the comedown of MDMA can also cause vivid delirious hallucinations in some people though even despite the feelings of clarity that come with the high. For me these have been mostly visual although they affect cognition in a deeper way than that too because I've seen people totally rambling mad like they were dreaming while awake and pantomiming activities from different locations they weren't actually at and stuff like that just from taking a few tabs and hitting the bong a few hours later. The shit can get really wonky if you're not careful.

Not sure what to say without the actual studies on this but am amazed that one person can be quite chill and another just the opposite on the same bud of weed.
Goes for most substances it seems. No one size fits all kinda thing.
I have felt all of the above effects posted at some point in my use of MJ... even the hallucination (which may need to be defined a little maybe). Seeings things that arent there? Who is to say it is not difinitively? We do not know that which we do not know. We can only sense about 10% of our surroundings it has been said. IDK
If hallucination entails seeing a situation from a different perspective or the like then yep IME it is hallucinogenic.

Cannabis is definitely hallucinogenic for a lot of people even though it seems to be a lower percentage. They say for instance it's more likely to be so if you have a condition like schizophrenia or bipolar disorder or a family history of it and stuff like that, and that's like at least 5% of the population right there, which may not seem like very much, but that's 400 million people worldwide, while the number of people who use cannabis worldwide is estimated to be around 200 million.

I use cannabis every day and have a high tolerance and still find it trippy, but in a muted way compared to when my tolerance is low. When I don't have tolerance or when I eat a potent edible when I've only been smoking, it is distinctly similar to psychedelics for me, although still not entirely the same, or necessarily even mostly the same. However, I have tried many different kinds of drugs and most of them were less similar to psychedelics than cannabis is for me in the way that cannabis is for me.

Kratom may be a 5HT2A antagonist and it makes me very tolerant to the psychoactive effects of THC. When i'm on kratom i can't get enough weed, and i always retain a sense of sobriety. I have even pushed it toward a cannabinoid overdose in the somatic department without getting enough, so to speak. The combination is rather enjoyable but not at all synergistic. Maybe kratom could let people with strong boundaries explore cannabis without some of the freakier effects. Personally i just love the freakiness and have never felt any analgesic or otherwise overtly "medical" effects from cannabis. To me the healing power is inseparable from the psychoactivity.

Mitragynine, from kratom, is actually also a 5-HT1A receptor ligand with significantly higher potency than at most other sites including opioid receptors according to PDSP binding data, as well as binding to some adrenergic and dopamine receptors at non-negligible concentrations. Kratom is significantly more complex than it's given credit for, and it's not simple even with respect to just its opioid activities either. It's hard to tell what's going on with it exactly, although that being said, I think it's worth noting that the 5-HT1A receptor activity may have an impact if it's agonism, as this mechanism is believed to reduce the negative effects of THC, including when induced by CBD, and I wouldn't be surprised if it contributes to the aforementioned impact of MDMA as well.

never have any visions from cana.just relax,munchees possible,enhanced feeling of rhytm,music...etc.....even analgesia in light form.nothin simmilar to psychedelics.its in separate category of substances for me....quite unique even-plant cannabis-buds&resin

People who are this way this should probably be glad for it. I love tripping on cannabis but it is not relaxing.

 

[Mjäll]

Here is the link to the study about cannabis acting through CB1-5-HT2A receptor heterodimers, I've seen it many times.

Cognitive Impairment Induced by Delta9-tetrahydrocannabinol Occurs through Heteromers between Cannabinoid CB1 and Serotonin 5-HT2A Receptors

Specific subtypes of cannabinoid and serotonin receptors interact to form heterodimers that mediate the cognitive deficits—but not the analgesic effects—induced by tetrahydrocannabinol, the major psychoactive constituent in Cannabis sativa.

journals.plos.org

There's logic to what you've proposed, although the first thing I have to ask is, have you considered using something like ∆8-THC instead? There are many people who specifically praise it for being an alternative to ∆9-THC with a less intense head trip and fewer dysphoric feelings. I haven't really kept up with the recent development of legal THC alternatives lately but I know there are many other options like it too. I have used ∆8-THC personally and definitely did find it lighter than ∆9-THC while still being similar, although reactions do vary from person to person as with any drug.

I ask mainly because getting something like ∆8-THC is going to be a lot easier than getting a selective 5-HT2A receptor agonist and a selective kappa-opioid receptor antagonist to mix with your cannabis, and require less use of experimental drugs in the process.



This is completely true, and it also gives you iron lungs. Smoking cannabis on the comedown of MDMA can also cause vivid delirious hallucinations in some people though even despite the feelings of clarity that come with the high. For me these have been mostly visual although they affect cognition in a deeper way than that too because I've seen people totally rambling mad like they were dreaming while awake and pantomiming activities from different locations they weren't actually at and stuff like that just from taking a few tabs and hitting the bong a few hours later. The shit can get really wonky if you're not careful.



Cannabis is definitely hallucinogenic for a lot of people even though it seems to be a lower percentage. They say for instance it's more likely to be so if you have a condition like schizophrenia or bipolar disorder or a family history of it and stuff like that, and that's like at least 5% of the population right there, which may not seem like very much, but that's 400 million people worldwide, while the number of people who use cannabis worldwide is estimated to be around 200 million.

I use cannabis every day and have a high tolerance and still find it trippy, but in a muted way compared to when my tolerance is low. When I don't have tolerance or when I eat a potent edible when I've only been smoking, it is distinctly similar to psychedelics for me, although still not entirely the same, or necessarily even mostly the same. However, I had tried many different kinds of drugs and most of them were less similar to psychedelics than cannabis is for me in the way that cannabis is for me.



Mitragynine, from kratom, is actually also a 5-HT1A receptor ligand with significantly higher potency than at most other sites including opioid receptors according to PDSP binding data, as well as binding to some adrenergic and dopamine receptors at non-negligible concentrations. Kratom is significantly more complex than it's given credit for, and it's not simple even with respect to just its opioid activities either. It's hard to tell what's going on with it exactly, although that being said, I think it's worth noting that the 5-HT1A receptor activity may have an impact if it's agonism, as this mechanism is believed to reduce the negative effects of THC, including when induced by CBD, and I wouldn't be surprised if it contributes to the aforementioned impact of MDMA as well.



People who are this way this should probably be glad for it. I love tripping on cannabis but it is not relaxing.

Cool! 5HT1A is a target for psychedelics and especially 5-MeO-DMT unless i'm mistaken. Seems to be implied in a oneness blessing type feeling.

Actually that same study didn't find activity at 5HT2A so i stand corrected.