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Pharmacology How drugs affect the workings of the human body.

 
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  #1  
Old 10-04-2009, 22:04
riaahacker riaahacker is offline
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wondering why cannabis is psychedelic

Swim has smoked weed and a few times has felt psychedelic effects, mainly dissociation, mild visual distortion, and heightened sensory perception. For awhile he's wondered why it would do this then he developed a hypothesis that would be interesting to try for himself or within a research setting. Cannabinoids through CB1 agonism have been shown to modulate the opioid system. Mu-opioid action causes a release of dopamine which explains the euphoria that comes, there is also k-opioid action which from selective k-opioid agonists like salvia has been shown to cause psychedelic, dissociative, and extreme visual effects. This might explain why THC has the psychedelic effects it has, partial k-opioid activation. He would like to see if a k-opioid antagonist stops these effects. Anyone else have any thoughts?

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This was a good question, stimulated good discussion
  #2  
Old 10-04-2009, 23:04
Gradient Gradient is nu online
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Re: wondering why cannabis is psychedelic

riaahacker,

Interesting topic! Also, those are some interesting relationships that you've speculated. The involvement of opioid systems may indeed contribute to the subjectively psychedelic activity of cannabinoids - good thinking there - , but perhaps there is a more direct culprit?
I'm glad that you've asked this question. It made me run out and search for some literature on the subject. Luckily, a thorough review article published in 2008 hits this topic pretty comprehensively by addressing the specific distribution of cannabinoid receptors in the retina, and all of the studies on the subject up until 2008. Please allow me to direct your attention to some relevant quotes:

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

"Acute effects of marijuana smoking on vision include a reduction in vernier and Snellen acuity, alterations in color discrimination and an increase in photosensitivity" (pg 507)

"Adams et al. (1978) stated that 'it consequently seems likely that marijuana or a metabolic product of marijuana acts directly on the retina to produce the delay in glare recovery. This suggestion of 30 years ago is now receiving much support and likely applies to the effects of marijuana on acuity and color vision." (pg. 507)

"CB1-receptor agonists stimulate monoamine oxidase in bovine retina and inhibit aspartate release. CB1-receptor mRNA was detected in rat retina by insitu hybridization...while CB2-receptor mRNA was reported in the retina of adult rats, but not in rat embryos." (Pg 507)

"Curiously, we found that CB1-receptors in dendrites in the OPL was exclusively to dendrites of the rod bipolar cells (plasma membrane) and not horizontal cells." (pg 509)

"WIN-55 reversibly inhibited (70%) of the L-type calcium current in salamander bipolar cells...Yazulla et al. (200) showed by electron microscopy that CB1 receptors were present on virtually all ON bipolar cells, but only about one-third of the OFF bipolar cells...Indicates that retrograde suppression of bipolar activity would be more of a factor with increments in light intensity than in decrements about the ambient background." (Pg 514)

"Electrophysiological studies show that endocannabinoids phresynaptically suppress the output of the 'through pathway' of the retina, photoreceptors and bipolar cells. The effect is subtle and modest as might be expected since smoking marijuana doens't render the smoker blind." (pg 519)

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

There's pretty much everything you wanted to know about cannabinoids and the retina. If you're still interested, I urge you to read the attached document; it's very thorough and quite interesting - it even covers the role of such receptors in development!

-G

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Very well written post and proof to back up statements. Good Job
very interesting indeed, good read
  #3  
Old 12-04-2009, 06:58
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Re: wondering why cannabis is psychedelic

I read the title and immediately thought of salvia and its mechanism over the opoid receptors before I opened the thread!!!!

I would have to imagine that it would be a specific cannabinoid compound directly responsible for the mild psychedelic properties. THC is doubtful to me, in studies pure tetrahydrocannabinol induces an extreme state of paranoia, but lacks distortions. There are many compounds in cannabis that are still not understood, there may be a cannabinoid which is strictly responsible for this, or perhaps the combination of them all is the producer of it.

Remember, you're dealing with the raw product, not isolated, purified THC. Consider opium, for example. Although the main mechanisms of action come from morphine and codeine, thebaine and papaverine are also present... and this is what gives opium its distinct high, seperate from pure morphine or codeine.
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Old 12-04-2009, 07:43
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Re: wondering why cannabis is psychedelic

The THC in cannabis binds to receptors which have points all over the body. They are used to regulate all kinds of things and thus the effects are quite scattered. It is one of the few compounds we label as both a stimulant AND a depressant. Because of this receptor binding however, it has many effects, some of which are psychedelic.

What is interesting about these receptors is that it almost seems like we evolved them over time ourselves, perhaps as a way to slow the body down when it is working itself too much. SwiM's dog Clue finds resin (scraped resin, not hash - Clue has yet to try hash) to be very psychedelic, moreso than the pot itself.
  #5  
Old 12-04-2009, 18:31
riaahacker riaahacker is offline
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Re: wondering why cannabis is psychedelic

All very interesting indeed

@Gradient

A very interesting concept to read about thanks for the file, a direct action on the retina, very cool

@Boca_Chick

It is known that other cannabinoids such as CBD regulate the metabolism of THC. The other cannabinoids definitely could contribute to this effect and I wish more research could be done on the matter.

Another thing I've seem to notice is that more people report that oral consumption seems to have more of a psychedelic effect than smoking. Maybe THC's active metabolite is something worth looking into, 11-hydroxy-THC, anyone have any info on this one?
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Old 21-04-2009, 14:05
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Re: wondering why cannabis is psychedelic

Swim tends to agree with greenport. Cannabinoid receptors are found all over the brain and probably have downstream effects on a wide number of neurotransmitter systems.

Swim thinks it's likely that k-opiate receptors are are involved but there's definitely more to it than that.Many people claim cannabis is much more psychedelic when combined with 5-htp and swim thinks this would point towards a serotonin related mechanism for psychedelia.

This study seems to suggest that the cannabinoid system does indeed have an effect on 5ht2a receptors;

http://www.ncbi.nlm.nih.gov/pubmed/17944876

As an interesting aside, swim thinks that instead of merely activating the opiate receptors cannabis somehow works to make your natural opiate releases stronger/seem stronger. For example if you laugh you'll get a large opiate release for a few seconds but then it dies back down.
You don't get a constant level of euphoria like you would with opiates.

Last edited by vinylmesh; 22-04-2009 at 13:40. Reason: sp
  #7  
Old 21-04-2009, 14:57
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Re: wondering why cannabis is psychedelic

Quote:
Originally Posted by riaahacker View Post
It is known that other cannabinoids such as CBD regulate the metabolism of THC. The other cannabinoids definitely could contribute to this effect and I wish more research could be done on the matter.

Another thing I've seem to notice is that more people report that oral consumption seems to have more of a psychedelic effect than smoking. Maybe THC's active metabolite is something worth looking into, 11-hydroxy-THC, anyone have any info on this one?
riaahacker,

I'd love to see the same kind of study! Apparently a handful of the medical cannabis dispensaries in California have begun work on such an endeavor; the classical indica/sativa categorization is old-hat now. Working with the newer classifications (afganica, sativa, kafiristanica, and indica), plants that have been identified as particularly psychedelic tend to be kafiristanicas (sour diesel, chem dawg, and other related plants). These are notoriously high in both CBN and THC. You're absolutely right; there has been some interaction demonstrated between the psychoactivity of the compounds in cannabis - these different levels likely account for the subjective differences in effects from plants of different genealogies. Here is a thread from this forum on the issue:

http://www.drugs-forum.com/forum/showthread.php?t=60861

It's an interesting dynamic that you highlight; when cannabis is orally ingested, the effects are consistently distinct when compared to smoked. Here is a study discussing the metabolism of THC to 11-ho-THC. There is clearly room for variability here; one individual may experience markedly psychedelic effects while another might consider the same sample of cannabis to be average in potency.

http://www.ukcia.org/research/Smoked...nAsthmatic.php

Here is a particularly relevant quote:

Quote:
"repeated exposure to marijuana is believed to lead to induction of enzymes needed to convert delta-9-THC to the active 11-hydroxy metabolite (19), less extensive metabolism of delta-9-THC to the active form in our asthmatic subjects with relatively little previous marijuana experience might have accounted for a lesser magnitude of physiologic effect than would have resulted had they been chronic users."
One has found absolutely no data regarding this last speculation, but one has been lucky enough to have conversations with a member of ongoing medicinal cannabis research regarding the potential role of delta-11-THC compared to delta-9-THC when orally ingested. Here is a cursory quote regarding the conversion of delta-9-THC to delta-11-THC in the liver:

Quote:
The Institute of Medicine published in its Mar. 1999 report titled "Marijuana and Medicine: Assessing the Science Base":
"A characteristic feature of the marijuana 'high' is a distortion in the sense of time associated with deficits in short-term memory and learning. A marijuana smoker typically has a sense of enhance physical and emotional sensitivity, including a feeling of greater interpersonal closeness. [...]
Delta-9-THC and Delta-8-THC are the only compounds in the marijuana plant that produce all the psychoactive effects of marijuana.
Because Delta-9-THC is much more abundant than Delta-8-THC, the psychoactivity of marijuana has been attributed largely to the effects of Delta-9-THC." [Editor's Note: When marijuana is metabolized in the liver, a new compound is formed. Called Delta-11-THC, it is more psychoactive than marijuana's other cannabinoids.


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Very interesting information and well written.

Last edited by Gradient; 21-04-2009 at 15:16.
  #8  
Old 21-04-2009, 15:09
psyche psyche is offline
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Re: wondering why cannabis is psychedelic

This is interesting thread. SWIM has from the beginning appreciated marijuana almost solely because of this psychedelic component and had very intense experiences with it.

Quote:
Another thing I've seem to notice is that more people report that oral consumption seems to have more of a psychedelic effect than smoking. Maybe THC's active metabolite is something worth looking into, 11-hydroxy-THC, anyone have any info on this one?
This is good point. When smoked, the metabolite 11-hydroxy-thc propably has little to do with effects, but it's completely different story when eaten:

Quote:
Oral bioavailability of THC, whether given in the pure form or as THC in marijuana, also is low and extremely variable, ranging between 5 percent and 20 percent (Agurell et al. 1984, 1986). Great variation can occur even when the same individual is repeatedly dosed under controlled and ideal conditions. THC's low and variable oral bioavailability is largely a consequence of large first-pass hepatic elimination of THC from blood and due to erratic absorption from stomach and bowel. Because peak effects are slow in onset and variable in intensity, typically at least an hour or two after an oral dose, it is more difficult for a user to titrate dose than with marijuana smoking. When smoked, THC's active metabolite 11-hydroxy-THC probably contributes little to the effects since relatively little is formed, but after oral doses the amounts of 11-hydroxy-THC metabolite may exceed that of THC and thus contribute to the pharmacologic effects of oral THC or marijuana.
http://www.medmjscience.org/Pages/reports/nihpt2.html

Also mentioned in the same site:

Quote:
Large doses of THC delivered by marijuana or administered in the pure form can produce mental and perceptual effects similar to drugs usually termed hallucinogens or psychomimetics. However, the way marijuana is used in the United States does not commonly lead to such profound mental effects.
Edit:

Quote:
Quote:
"repeated exposure to marijuana is believed to lead to induction of enzymes needed to convert delta-9-THC to the active 11-hydroxy metabolite (19), less extensive metabolism of delta-9-THC to the active form in our asthmatic subjects with relatively little previous marijuana experience might have accounted for a lesser magnitude of physiologic effect than would have resulted had they been chronic users."
The site I was reading seems to suggest the opposite:

Quote:
Frequent and infrequent marijuana users are similar in the way they metabolize THC (Agurell et al. 1986; Kelly and Jones 1992).


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Gret post! Excellent points and good evidence/support. Your contributions here are greatly appreciated.

Last edited by psyche; 22-04-2009 at 22:17.
  #9  
Old 22-04-2009, 20:35
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Re: wondering why cannabis is psychedelic

Cannabis (KannaBosom) is psyhedelic because it is the true sacrement of christ. It is THE psychedelic~its NOT a drug, OR a hallucenogen like it is said to be by scientists/society/whoever~
when utilized with sincere respect Kannabosm completely and utterly cures all. It complete destroys the ego (again, Im talking if utilized mindfuly--hahaha i really mean mindLESSly but you should catch my drift. It opens the third eye and allows for a death/rebirth experience. It helps us to see or to remember who we REALLY are ~~if you can simply let go cannabis will help yhou to see the light within and realize the completeness of existence, of god~~and you will be blessed of mother earth as well.

when you properly aproach a plant teacher (or fungi or animal or rock or whatever it mayh be) YOU get to experience the plants existence while it simoutaneously experiences yours.

and as KannaBosm (the proper/biblical name for the plant which christ used to annoint people and heal them spiritualyh as well as phyicaly. Kannabosm is attributed with yhealing of leapors (cannabis has POWERFUL antibiotic properties) exercising demons (canna is a powerful anti-epileptic) curing glaucoma-curing EVERYTHING
I believe that CHRIST: IS the HIGH. i mean think about what the word HIGH means--It means bliss, it means mystical union, it means hapiness, it means you are one with yourself/god/universe it is the ONLY TIME we humans DIRECTLY connect wityh god;
and that is why its use as a sacrement is mandatory to my spirituality/well being. it is gods true sacrement.
ok so if the HIGH IS Christs spirit, if christ is a state of being that is the high, (the reason being that the Tree of Knowledge of Good and Evil IS KANNABOSM--and through partaking of it adam and eve became as God knowing duality/death etc. before this death was NOT a reality because they did not Know of it. DEATH is a HUMAN illusion and nothing more. but now understanding that life and death exist, good and evil, dark and light, etc--Man kinds ego was completely destroyed and he knew ONLY god (pure truth/love) but this act also lead to the human conditi0n (which IS nessesary for spiritual development and part of gods plan) tyhe condition being that humans THROUGH desire have hypnotized themselves with their body.....tyheyh are addicted to it they are just mind/ego......and so we are in perpetual cycles of pain (human existence=pain) because we are too addicted to Dopamine....addicted to our body actualy. we are too afraid to let go of it. but, this addiction-(all humans ARE in addiction-unless they are enlightened (awake) is ACTUALY a built in survival mechanism. we fuck alot and eat alot of fatty foods (both VERY rewarding dopamine wise) and that has helped us to survive. AND its helped to maintain our Maya (illusion)

SO-if christ is the high from cannabis (direct landline to god) then Christs body, as explained in the new testament, IS the Cannabis plant-christs holy gift to the world was that his body would remain FOREVER present in our existence/world. and the plant is forever present and it shows us god and it yhas the power to SAVE our world Literaly. i cant yhelp but wonder when bible speaks of the "Leaves of the Tree shedding fourth over ALL nations of the world HEALING them"
canna has the power to help people meditate, it alleviates numerous sicknesses, it DOES have tyhe ability to reverse the greenhouse effect entirely, not to mention save our rainforests AND OUR ECONOMY (its worlds NUMBER ONE cash crop) not to mention fact that hempseed is so healthy you could live off of it (literaly and be healthy), it also would eliminate all need for petrolium products feed the world quit using trees FUCK!!!!!!!! its so endless. thats why i say it is the tree in the bible-it was profesied that it would become illegal and that people would put pursecute eachother for using it (because it gives you REAL truth and healing and our gov is NOT ok with that)
i believe it can save our ass if we turn back to nature and too god.

Whyh is pot psychedelic? wy is grass blue or sun green? (oh, wait lol) It is a Gift from mother earth. completely non toxic, actualyh AMAZING medicine VERY ANTI-Cancerous, it makes people feel good makes their pain and nausea leave it helos glacoma and asthma and on top of that it just smells looks feels and tastes SOOOO incredibly beautiful that it is obviouslyh a gift from god. it makes me grin just to hold a couple big ounce cola christmas trees or even one tiny bud and stare at the thrichs for HOURS!!! hahah honestly sometimes i almost cant bring myself to smoke it cuz its too pretty but i always end up.....haha

Ok I know this was long and all, but as a Cannabis Minister, and the man who started Thc Ministry in wyoming, I wanted to let you all know that the hyigh from canna Is the most intense and perfected Medicine/psychedelic I have EVER came across--and trust my alligator when yhe straight up tells yhou tyhat yhe yhas tripped yharder off cannabis tyhan off ANYH otyher drug, and tyhis gator YHonestlyh yhas done EVERYH drug that a normal person could imagine. hes just missed a few weird head meds and a COUPLE research chems--that are AVAILABLE (i mean they Exist) hes done every high you can think of and he SWEARS on his life that cannabis shows you yourself even better than mushrooms do. and thats saying alot. I personaly wittnessed him eat 250 hits of LSD-25 (VERY GOOD PAPER!!! Radiated like a mofo under some blacklight anyway but lsd is not intense or real like green....NOT EVEN ANYHWYHERE close to shrooms. wyhile acid IS GREAT FUN!!!! I mean AMAZING fun and one of tyhe funnnest chems in exitence....it just LACKS that natural Realness/intensity Ive NEVER had a ++++ on LSD I dont tyhink its possible for myh gator. Ive had ++++ ONLY, and ONLY on Cannabis, Mushrooms, and DXM (no joke I even prefer it to phencyc i like k but its too hard (impossible) to obtain anymore.....well I dont reallyh tuss too mucyh anyhmore but it was tyhe love of myh life and DEFINATLYH yhas tyhe power to throw yhou into a K-hole-ish ego MIND FUCKING ego death/BEAUTIFUL SACRED experience...infact I think its even better than k. yep i said it shoot me. It lasts......but k is also amazing and DEFINATLY will give yhou a plus 4.

ok SORRY tyhis was so long. just wanted to make the point, that tyhe HIGHEST my alligator yhas EVER been in his life, the most fucked up hes ever been, the most lucid, the most deep hardcore hallucenation (mostly from eating it) the most REAL RAW truths--have come from Kanna. nothing else completely shows me god like that and cures me of any ailment
PRAISES TO JAH!!!!!!!!!!!!!!!!!!!!

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pretty full of offtopic; this is in the pharmacology forum, not euphoric mind :/
Is posting sth so crazily captivating but in a wrong forum deserving infraction? Cmon, cheer up.
This post is irrelevant to the question. Please post in the appropriate forum.
  #10  
Old 22-04-2009, 23:08
psyche psyche is offline
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Re: wondering why cannabis is psychedelic

So what would be the central mechanism through which cannabinoids cause hallucinogenic effects?

The more traditional 5-HT -pathway, to which I don't see very strong connection, or the more atypical psychedelic pathway through kappa-opioid receptor?

One study seems to suggest that kappa-opioid receptor activity would be responsible for dysphoric effects of THC, whereas mu receptor would be for euphoric. The absence of mu-opioid receptors prevents the place preferation for mice, whereas absence of kappa receptors abolishes place aversion and unmasks place preferation: http://www.jneurosci.org/cgi/content/abstract/22/3/1146

The 'weirdness' or 'abstractness' might be attributable to kappa-opioid receptors, which could make all places look equally new(or interesting).

The wikipedia entry of kappa-opioid-receptor has this to say about cannabis:

Quote:
The active component of cannabis, THC, is a partial kappa-opioid agonist and may account for the aversive affects of "paranoia" experienced during its use as well as some non-addictive properties of cannabis.
  #11  
Old 22-04-2009, 23:46
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Re: wondering why cannabis is psychedelic

psyche,

If I were a bettin' man, I'd put my money on multiple sources of receptor-activity (serotonergic, opioid, calcium currents) derived from cannabis summing together to elicit a psychedelic output - each contributing a characteristic of the experience. The article I posted above proposes several different roles that endogenous cannabinoids play in the visual pathway - the most relevant to this discussion is the inhibition of L-type calcium currents on bipolar rod cells by cannabinoids - they suggest that this would have direct consequences regarding perception of light levels (classic cannabis overall color enhancement).

However, the kappa opioid activity can't be ignored, as you astutely point out. This could only enhance the already occurring psychedelic activity due to the direct activity of cannabinoids on the retina. In terms of temporal summation - the effects of increased levels of cannabinoids directly on the retina, coupled with the amplified kappa opioid activity (though not as severe as salvia), would likely induce an atypical psychedelic state of consciousness. I think you're spot-on in attributing the 'weirdness or abstractness' to kappa activity; electrophysiological changes at the level of the retina alone can't be sufficient induce the cognitive psychedelic effects of cannabis.

In other words, since serotonergic and opioid activity have been attributed to cannabinoids - I wouldn't be surprised if both likely contribute to the psychedelic effects. Therefore, variations in levels of different cannabinoids that elicit different effects between plants would cause some plants to be more psychedelic than others. Now - to find the DMT strain of cannabis...

This has been a fun discussion!
  #12  
Old 23-04-2009, 00:58
psyche psyche is offline
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Re: wondering why cannabis is psychedelic

When we are talking cannabis, it is indeed most likely many factors together. The inhibition of calcium currents in retina, kappa-opioid receptor activation and possibly release of dopamine play a role in psychedelic effects, but I believe serotonergic system isn't involved in psychedlia. It would rather be involved with the anxiolytic effects of cannabis, acting on 5-HT1A receptors:

http://www.sciencedirect.com/science...0d3c9f3cc7f395

However, here is some data showing that cannabinoids inhibit the 5-HT2a mediated behaviour. This is the receptor subtype along with 5-HT2c which mediates the classic hallucinogenic response:

http://www.ncbi.nlm.nih.gov/pubmed/1...?dopt=Abstract

I think the psychedelic effects of cannabinoids is not related to classical hallucinogenic pathways, at least at the receptor level. Maybe there can be found a close connection when looking the situation neuroanatomically, considering complete functional brain parts/systems and receptor distribution on these?
  #13  
Old 23-04-2009, 01:38
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Re: wondering why cannabis is psychedelic

psyche,

Good point to bring up; the action of cannabinoids at serotonergic receptors is antagonistic. This, however, doesn't render these effects insignificant to the psychedelic experience. I'd urge you to take a closer look at the article you've cited. Specifically pages 5 and 6; please allow me to direct your attention to the specific statements that caught my attention regarding the posited inhibition of psychedelic activity by cannibinoids:

"On the contrary, the capacity of DOI to produce back-muscle contractions was potentiated by HU-210 pretreatment. The latter authors suggested that either different subtypes of 5-HT2 receptors are responsible for the production of these behaviors or the same 5-HT2 receptor subtype utilizes different signal transduction mechanisms to produce such differential actions...Thus, it seems more probable that back-muscle contractions produced by DOI in the rat are mediated via the activation of 5-HT2c sites, whereas the 5-HT2a receptor is responsible for the production of other discussed behaviors in both species."

I'm not sure this study is fully conclusive in identifying cannabis as a direct antagonist of serotonergic activity, let alone psychedelic activity. Their data is behaviorally based, and they highlight the problems with generalizing such data to human neuropharmacology.

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

I absolutely agree, however, with your overall point. The psychedelic component of cannabis is certainly atypical, the effects of which are likely mediated far more by different neurotransmitter systems than those utilized by the phenethylamines/tryptamines, such as those discussed above. However - the role of serotonin can't be ignored here (it rarely can be!). Even if the action is antagonistic, the repercussions of these actions can't be disregarded when discussing the quality of the psychedelic experience.

There is another cognitive effect that characterizes endogenous cannabinoids: depolarization-induced suppression of inhibition (DSI). This is a very complex dynamic that occurs in hippocampal pyramidal neurons. An almost reprehensibly brief summary of this activity is that endocannabinoids are responsible for modulating the percieved significance of incoming sensory experiences, inhibiting the memory of cognitively insignificant events while selecting for particularly salient memories. In other words, endocannabinoids are responsible for maintaining the signal-to-noise ratio in the hippocampus. Their primary mechanism of action is retrograde inhibition of calcium influx into the presynaptic element. Attached is a document that has a terrific illustration of this dynamic on page 2.

The authors of a related study suggest that this dynamic would serve to render every sensory stimuli to be 'monumentally magnificent', and associations between ideas and different stimuli may be enhanced. For example, an increased (or altered, really) sensitivity to music might be expected from this dynamic. Also, 'zoning out' would be a general behavioral state that might be expected - allowing the mind to drift from thought to thought with no real gating mechanism to determine which thoughts are significant and demand conscious attention.
I guess the point is, endocannabinoids are implicit in such wide-ranging functions that this discussion could go on for an extremely long time trying to identify the different components of the neural activity that characterize the compounds, and trying to speculate as to what increased presence of cannabinoids would do to each particular system. This has been a pretty good start, in my opinion!

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Old 23-04-2009, 01:43
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Re: wondering why cannabis is psychedelic

I'm hoping this post is automerged!

For some reason, the pdf didn't attach to my prior post. Here it is.
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File Type: pdf The Grass Roots of Synapse Suppression.pdf (157.6 KB, 13 views)
  #15  
Old 23-04-2009, 02:19
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Re: wondering why cannabis is psychedelic

That concept of DSI seems very interesting and could relate to a lot of cognitive effects of cannabis intoxication indeed. Must take a closer look at it tomorrow.

Quote:
I'm not sure this study is fully conclusive in identifying cannabis as a direct antagonist of serotonergic activity, let alone psychedelic activity. Their data is behaviorally based, and they highlight the problems with generalizing such data to human neuropharmacology.
Yeah, you're right. I guess it would be much more accurate to study genetically modified mice that lack those certain subreceptors compared to those that don't(if they can be so selectively eradicated?). Would that be the most reliable method of proving one's point? Mind you I'm no expert on methodology, I haven't learned different methods systematically. Wonder what in vitro studies would say about the binding affinity of THC to these subreceptors...

Oh, and how did you find pages 5 or 6 The link I put up only has an abstract.
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Old 23-04-2009, 03:01
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Re: wondering why cannabis is psychedelic

psyche,

You're absolutely right, that would be an amazing study! It's certainly feasible, though researchers would likely begin with more simple organisms then mammals to start out with - just to make sure that the mutations aren't fatal. At first I figured that it'd likely be difficult to find a fully sequenced organism that develops through life-cycles on quickly enough of a time-scale to be amenable to genetic research - that also actually expresses the same cannabinoid receptors that humans do. However, I quickly found that the evolution of the cannabinoid receptor has been studied.

Attached is an article that discusses the descent of the CB1 and CB2 receptors in invertebrates - apparently everything from onychophorans (large worms with legs), crustaceans, and nematodes express cannabinoid receptors. If I had my way, I'd likely begin with genetic knockouts for the CB1 receptor in a nematode, or a flatworm of some kind, to see exactly what functional deficits arise. That'd demand some serious funding, but it would be a great study.

If you'd like, I have no problem uploading the PDF that you linked to, or I can simply upload it to the file archive (if it isn't there already). The point you bring up is a good and significant one, and this article discusses the point quite nicely; very nitty gritty agonist/antagonist pharmacology. I just didn't want to upload a document that you had found - figured that's kind of like stepping on someone's toes/stealing someone's thunder...etc... I have no problem sending it to you, if you'd prefer. Thanks for finding it.
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File Type: pdf Cannabinoid receptors in invertebrates.pdf (136.2 KB, 9 views)

Last edited by Gradient; 23-04-2009 at 07:36.
  #17  
Old 23-04-2009, 09:54
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Re: wondering why cannabis is psychedelic

^^ Please do upload the study entirely. This thread had offered a lot of insight into psychedelic effects of cannabis. At the beginning I was in disbelief about opioid-system really playing a role in this, but it seemed to be the case after all. Serotonin system isn't involved as directly, but has at least it's role in anxiolytic effects and maybe in the psychedelic effects too, through ways unknown for know. The bipolar rods in the eye's are directly affected, so they play a role definately. And the DSI has it's own effects as a higher level, cognitive pattern that causes confusion, but also rapidly changing thoughts and a little bit dreamlike state.
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Old 23-04-2009, 20:24
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Re: wondering why cannabis is psychedelic

My apologies for the delay. Attached is the second article psyche cited. I only just realized this, but I've actually had the privilege of meeting Nissar A. Darmani, the principle researcher of this study - currently a professor at NYU (I don't attend NYU - he came to my university to speak). Extremely amiable guy who was actually one of the pioneers to study the potential for cannabinoids to alleviate nausea associated with chemotherapy in cancer treatment. He's making huge strides to link genetic polymorphisms to schizophrenia. Definitely a very bright light in the world of neuroscience.

Cool find psyche!

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Old 23-04-2009, 22:29
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Re: wondering why cannabis is psychedelic

Sorry if I don't copy and paste 10 pages of information the the poster doesn't even understand (cough, a few responses above...) - as i've actually read about the topic. I'll type the basic method of action and some information (without coppying some online site!! Gasp!!!).

It's sorely disappointing to see 10,000 word responses coppied directly off a site - blue hyperlinks and all...

Delta-9-tetrahydrocannabinol (short hand is THC) is the active ingredient in marijuana (common knowledge). Though, lesser known, THC is the trans- geometric isomer (the rotated molecuel, rather than the optical dextro-and levo-). This aids in the crossing of the big 3B's - blood brain barrier.

Once passing into the brain, THC stimulates the release of endocannabinoids which agonize CB1 and CB2 receptors as a primary method of action - concentrating in the prefrontal cortical pathways (orbitofrontal cortex, controlling higher-level abstract emotions; and specifically the left orbitofrontal region which relieves anxiety when active) and in the visual cortex (visual hallucinations/distortions).

This isn't THC's only effect. It also, similar to terterairy amines like morpihine, stimulates the -opoid receptors - consequently causing a release of dopamine in the nucleus accumbens (pleasure center).

It's activity on -opoid receptors is evident by the opiate-overdose treatment drug naloxone. (Taking naloxone will kill your pleasurable encounter with marijuana )


The reason one is paranoid after smoking marijuana is that, though phenethanolamine (sp?) and N-methyltransferase, all the dopamine is converted to epinephrine/adrenalin which fuels anxiety.

Hope it helped,

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  #20  
Old 23-04-2009, 22:53
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Re: wondering why cannabis is psychedelic

Quote:
Originally Posted by eche05 View Post
Sorry if I don't copy and paste 10 pages of information the the poster doesn't even understand (cough, a few responses above...) - as i've actually read about the topic. I'll type the basic method of action and some information (without coppying some online site!! Gasp!!!).

It's sorely disappointing to see 10,000 word responses coppied directly off a site - blue hyperlinks and all...

Delta-9-tetrahydrocannabinol (short hand is THC) is the active ingredient in marijuana (common knowledge). Though, lesser known, THC is the trans- geometric isomer (the rotated molecuel, rather than the optical dextro-and levo-). This aids in the crossing of the big 3B's - blood brain barrier.

Once passing into the brain, THC stimulates the release of endocannabinoids which agonize CB1 and CB2 receptors as a primary method of action - concentrating in the prefrontal cortical pathways (orbitofrontal cortex, controlling higher-level abstract emotions; and specifically the left orbitofrontal region which relieves anxiety when active) and in the visual cortex (visual hallucinations/distortions).

This isn't THC's only effect. It also, similar to terterairy amines like morpihine, stimulates the -opoid receptors - consequently causing a release of dopamine in the nucleus accumbens (pleasure center).

It's activity on -opoid receptors is evident by the opiate-overdose treatment drug naloxone. (Taking naloxone will kill your pleasurable encounter with marijuana )


The reason one is paranoid after smoking marijuana is that, though phenethanolamine (sp?) and N-methyltransferase, all the dopamine is converted to epinephrine/adrenalin which fuels anxiety.

Hope it helped,
eche05,

Can you please clarify as to how any of this neural activity generates psychedelic effects? Most of this information is valid (though quite general), but I fail to see your point in suggesting that any of this activity generates subjectively psychedelic states. Please draw a more explicit correlation between CB1 and 2 receptor activation, -opioid receptor activation, and dopaminergic activity, and the generation of the above-described atypical psychedelic states.

Also, that seems to be a needlessly confrontational post - let alone, quite redundant. I'm not sure exactly what you're criticizing. Had you taken the time to read through prior posts, you'd know that the majority of this information had already been stated - in greater detail than in your own post. Was the sarcasm necessary? Remember, sarcasm is rarely even remotely as effective on the internet as it is in person. Generally, sarcasm on the internet appears slightly condescending and hostile. The purpose of posting one's source is to allow other members to judge the validity of the source for themselves, rather than rely solely upon the member communicating the information. This is a standard for good discussion, and is not a form of plagiarism (if that's what you're implying).

I'd love to see some data supporting any correlation you draw between the above mentioned cannabinoid activity and psychedelic states! It would be extremely useful (and exciting) to have a study that confirms such a relationship, and it's been hard for me to find one. Also, do you have any data so support the suggestion that all dopamine agonized by cannabinoids is converted to norepinephrine or epinephrine? There is no specific 'pleasure center' in the brain; rather, there are now at least 3 suggested circuits of neurons dedicated to generating different kinds of reward. Dopamine is converted to norepinephrine first (by DA--hydroxylase), and then to epinephrine by the enzymes you discussed. I would assume that MAO would gobble any dopamine that has already bound to receptors - enzymatically degrading it before any other synthesis-oriented enzymes might have a chance. Aren't those enzymes located specifically in vesicles at noradrenergic synapses? I don't see how this can be a major contributor, but I'd love to see a study to learn me wrong!

Last edited by Gradient; 23-04-2009 at 23:17.
  #21  
Old 23-04-2009, 22:58
psyche psyche is offline
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Re: wondering why cannabis is psychedelic

The copy&pasted parts aren't especially lengthy, only the part needed to explain the scheme is pasted. There is also commentary and context posted to the pasted text, not only throwing things as a fact because it's scientific study. The OP should understand what is being posted since this is a pharmacology forum. There is no simple answer. It's also a matter of constant debate to evolve information. There are also much summary wrote in the above posts that should make it clear.

Quote:
This isn't THC's only effect. It also, similar to terterairy amines like morpihine, stimulates the -opoid receptors - consequently causing a release of dopamine in the nucleus accumbens (pleasure center).
This hasn't yet been covered in this topic. Dopamine certainly plays a role, as excess dopamine is tied to scizophrenia.

Quote:
The reason one is paranoid after smoking marijuana is that, though phenethanolamine (sp?) and N-methyltransferase, all the dopamine is converted to epinephrine/adrenalin which fuels anxiety.
True, and as commonly is known THC causes a release of norepinephrine too.
  #22  
Old 23-04-2009, 23:25
eche05 eche05 is offline
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Re: wondering why cannabis is psychedelic

Quote:
Originally Posted by Gradient View Post
eche05,

Can you please clarify as to how any of this neural activity generates psychedelic effects? Most of this information is valid (though quite general), but I fail to see your point in suggesting that any of this activity generates subjectively psychedelic states. Please draw a more explicit correlation between CB1 and 2 receptor activation, -opioid receptor activation, and dopaminergic activity, and the generation of the above-described atypical psychedelic states.

Also, that seems to be a needlessly confrontational post - let alone, quite redundant. I'm not sure exactly what you're criticizing. Had you taken the time to read through prior posts, you'd know that the majority of this information had already been stated - in greater detail than in your own post. Was the sarcasm necessary? Remember, sarcasm is rarely even remotely as effective on the internet as it is in person. Generally, sarcasm on the internet appears slightly condescending and hostile. The purpose of posting one's source is to allow other members to judge the validity of the source for themselves, rather than rely solely upon the member communicating the information. This is a standard for good discussion, and is not a form of plagiarism (if that's what you're implying).

I'd love to see some data supporting any correlation you draw between the above mentioned cannabinoid activity and psychedelic states! It would be extremely useful (and exciting) to have a study that confirms such a relationship, and it's been hard for me to find one. Also, do you have any data so support the suggestion that all dopamine agonized by cannabinoids is converted to norepinephrine or epinephrine? There is no specific 'pleasure center' in the brain; rather, there are now at least 3 suggested circuits of neurons dedicated to generating different kinds of reward. Dopamine is converted to norepinephrine first (by DA--hydroxylase), and then to epinephrine by the enzymes you discussed. I would assume that MAO would gobble any dopamine that has already bound to receptors - enzymatically degrading it before any other synthesis-oriented enzymes might have a chance. Aren't those enzymes located specifically in vesicles at noradrenergic synapses? I don't see how this can be a major contributor, but I'd love to see a study to learn me wrong!

I'll draw a better connection. And yes, you're right, it was a bit confrontational. I was a bit tired of people (not you, but the poster near the top) who just copy and pasted about 10 pages of information - mostly illedgable by the general public and recieving praise for pressing 2 keys. Just felt that myself (and the public) was a bit cheated

You, obvious by your response, know your pharmacology; though to address the general audience (the majority...), generality is prefered over excessive specifity.

To address your valid (and true) point about not quite drawing the connection, i'll elaborate (never hurts ). Actually, I have soccer, though I promise to post an elaboration.

eche05 added 1 Minutes and 25 Seconds later...

Quote:
Originally Posted by psyche View Post
The copy&pasted parts aren't especially lengthy, only the part needed to explain the scheme is pasted. There is also commentary and context posted to the pasted text, not only throwing things as a fact because it's scientific study. The OP should understand what is being posted since this is a pharmacology forum. There is no simple answer. It's also a matter of constant debate to evolve information. There are also much summary wrote in the above posts that should make it clear.

This hasn't yet been covered in this topic. Dopamine certainly plays a role, as excess dopamine is tied to scizophrenia.

True, and as commonly is known THC causes a release of norepinephrine too.
Sorry for overgeneralizing, I was mostly directing it at one poster near the top. You're fine - pasting is helpful to assert source validity as well.

Last edited by eche05; 23-04-2009 at 23:25. Reason: Automerged Doublepost
  #23  
Old 23-04-2009, 23:51
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Re: wondering why cannabis is psychedelic

swim has heard that taking a capsule of honey oil(butane hash) that has been isomerized (all the cannabonoids were converted to Delta-6 THC) , some people thought they had been slipped something else like LSD because of the psychedelic effects.

Here is an exert from Marijuana Chemistry by Michael Starks:

Quote:
When pure, THC is roughly three times more potent when smoked when eaten. Smoking about 6mg, or eating about 15mg, of THC will feel like a minimal high to most people; whereas smoking 30mg or eating 75mg will tend to produce very intense effects, comparable to those from LSD. However, when hashish or marijuana is eaten, it may be five or ten times less potent than smoking due to incomplete absorption from the intestine.
  #24  
Old 24-04-2009, 01:41
eche05 eche05 is offline
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Re: wondering why cannabis is psychedelic

Quote:
Originally Posted by Milk man View Post
swim has heard that taking a capsule of honey oil(butane hash) that has been isomerized (all the cannabonoids were converted to Delta-6 THC) , some people thought they had been slipped something else like LSD because of the psychedelic effects.

Here is an exert from Marijuana Chemistry by Michael Starks:
True. However, there's much better (and helthier) alternatives to smoking the THC plant and all. And it's reeeeaaally simple - while simultaneously cutting the lung-associated problems easily by a 50th.
  • Take the weed, and add an equal ammount of acetone (nail polish remover), benzene, hexane, butane, paint thinner, or any other hundreds of easy, lying around organic solvents.
  • Shake the hell out of the mix of the weed and solvent, and leave to sit for a few days (to get almost 100%. Just shaking it for 5 minutes still gets upwards of 70% - higher than the percentage when smoking the plant!)
  • Pour it through a rag or sock, to seperate the weed and solvent. Evaporate the solvent. SWIY now has pure THC - greaaat stuff.


(to make it on topic: this increases the absorbtion because you're lungs aren't filled up with useless other smoke particles like nitric oxide)
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Old 24-04-2009, 19:02
Milk man Milk man is offline
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Re: wondering why cannabis is psychedelic

Quote:
Originally Posted by eche05 View Post
True. However, there's much better (and helthier) alternatives to smoking the THC plant and all. And it's reeeeaaally simple - while simultaneously cutting the lung-associated problems easily by a 50th.
  • Take the weed, and add an equal ammount of acetone (nail polish remover), benzene, hexane, butane, paint thinner, or any other hundreds of easy, lying around organic solvents.
  • Shake the hell out of the mix of the weed and solvent, and leave to sit for a few days (to get almost 100%. Just shaking it for 5 minutes still gets upwards of 70% - higher than the percentage when smoking the plant!)
  • Pour it through a rag or sock, to seperate the weed and solvent. Evaporate the solvent. SWIY now has pure THC - greaaat stuff.


(to make it on topic: this increases the absorbtion because you're lungs aren't filled up with useless other smoke particles like nitric oxide)

IS SWIY CRAZY???!?!?! Using paint thinner for an extraction? Or nail polish!? Swim was talking about butane hash, not about smoking.

The post made by eche05 should be disregarded as it is VERY DANGEROUS and potentially life-threatening. The product will be anything BUT pure. What if the solvent doesnt evaporate fully or leaves other residues behind.

Last edited by Milk man; 24-04-2009 at 19:08.

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