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What pharmacologically makes synthetic cannibanoids so unsafe vs THC?

C

cannibalsnail

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Sep 18, 2011
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I understand that compounds such as JWH are full agonists whereas THC is a partial agonist but why does this make them so dangerous? In all honesty I am not so sure what exactly is bad about them except for their tendency to cause panic attacks etc. I know there have been a few deaths, why would a full agonist make this possible when THC partial agonist make it essentially impossible. Differing Phospholipase ratios?
 
Full agonists simpy activatc CB1/2 more than THC does, as a result most of the side effects are an exaggeration of the normal side effects profile of THC. For instance extreme paranoia, vomiting etc are known with THC but for the most part it requires massive oral doses - on the other hand it can be achieved from as little as 1-2g of illicit "spice". In addition, since the full agonists activate the receptor much more strongly than your body's internal endocannabinoids can they will probably produce "classical" tolerance and withdrawal symptoms more than partial agonists. This has been somewhat confirmed because some users report loss of appetite, sleep issues etc after discontinuing moderate-term use of JWH.

An analogy is the effects of buprenorphine versus morphine. Morphine is a full agonist and produces much more euphoria, breathing depression etc, than buprenorphine, although both will produce opioid effects in naive users. W/d from bupe is going to be comparatively easier than w/d from full agonists.

Another would be the benzos versus barbs thing - one can think of benzodiazepines as "partial agonists" for the GABA site where barbiturates are more "full agonists". Both produce similar effects but barbiturates produce a much stronger effect per given dose.
 
Sekio is right.
Since synthetic's can activate CB1R's so strongly, they can even cause seizures.
Also, THC ingested via cannabis is augmented by many other cannabinoids like cannabidiol, unlike synthetic cannabinoids.
 
Personally I prefer the full agonists I have tried, CP55,940, and HU-210 are favourites of mine. Damn shame they are so hard to get hold of now.
Although HU-210 produces a VERY rapid tachyphylaxis-after a single dose even. Although Its also very long acting.
 
It is wise to note that essentially all of the cannabinoids from Cannabis spp. are partial agonists (THC, CBN) or antagonists (CBD, cannabivarins). Perhaps that explains the relative safety of cannabis vs JWH.

Also, John Huffman himself said that these compounds are pretty poor recreational drugs with respect to safety margins.
 
Does anyone know if there has been any research done into addiction of the synthetics?

I know of at least one person who uses one (I believe K2) and acts on it in a similar manner I've heard how heroin users act.

He'll smoke it, nod out for about 15 to 30 minutes, wake up, smoke it again, nod out, and repeat the whole process for hours.

When he doesn't have it, he's really irritable, gets extremely stressed and can't sleep. Spends most of his money on it.

I have always been under the impression THC does not give users a physical dependency addiction, but can give them a psychological addiction (preferring to be in the state all the time).

Do some of the synthetic cannibinoids carry a risk of physical addiction?
 
sekio said:
In addition, since the full agonists activate the receptor much more strongly than your body's internal endocannabinoids can they will probably produce "classical" tolerance and withdrawal symptoms more than partial agonists. This has been somewhat confirmed because some users report loss of appetite, sleep issues etc after discontinuing moderate-term use of JWH.
Click to expand...

There's plenty of anecdotal reports of JWH/spice addiction in the Cannabis Discussion forum & on Erowid.
 
This is coming from someone who was high on AM-2201 for 6 months all day almost every day: They're much more addictive than THC, I'd put it on the same level of amphetamine for addictiveness, they have a higher chance of inducing paranoia in some people(although this is because it's easy to OD on, if you never OD this will never be an issue), and they're full agonists of the CB receptors, so you feel much more "drained" when it wears off. (That was part of why they're so addictive, when they wear off you feel totally spent and drained and you need more if you want to actually move.). I wouldn't call them UNSAFE anymore than any addictive drug, but they're a much worse thing to be addicted to when compared to weed.
 
Yeah, as mentioned above, it's full agonism (many JWH compounds) versus partial agonism (THC) along with altered C1/C2 receptor affinity ratios that probably account for the different effects of the new synthetic cannabinoids. This same variability problem for full versus partial agonism is observed with DOx compounds (often full agonists) versus LSD/psilocin (partial agonists); full agonists at the 5HT2A receptor often cause more severe vasoconstriction and have poorer therapeutic ratios (therapeutic dose : lethal dose).
 
JackiesBabyy said:
This is coming from someone who was high on AM-2201 for 6 months all day almost every day: They're much more addictive than THC, I'd put it on the same level of amphetamine for addictiveness, they have a higher chance of inducing paranoia in some people(although this is because it's easy to OD on, if you never OD this will never be an issue), and they're full agonists of the CB receptors, so you feel much more "drained" when it wears off. (That was part of why they're so addictive, when they wear off you feel totally spent and drained and you need more if you want to actually move.). I wouldn't call them UNSAFE anymore than any addictive drug, but they're a much worse thing to be addicted to when compared to weed.
Click to expand...

Ah yeah I did the same, was more like 10 months though and by the end my doses were 150mg a time and more if I wanted to actually feel high compared to feeling "ok" and "sane". A month of hellish withdrawals later and I was almost back to what I hope is normal. XD

Definitely something to be careful of that drug. Far too damn strong. Can really fuck with bowel movements and body hydration distribution if you get into heavy doses/long runs.

The seizure risk is possibly overstated IMO as many people automatically think that convulsions = seizures. From coming off of it and seeing the effects of massive antagonism/underagonism at those receptors, it was equally as severe as an overdose but in the opposite "polarity" of shakes and forced muscle motion and tension. Hard to explain as it is a very specific psychosomatic response. The best I could describe the most noticeable muscle tension was wanting to move my fingers back
 
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It would be nice if we eill found a partial agonist among the new synthetics, these full agonists are damn strong.
Do not smoke it daily, give your body time to cleanse from it. Buy some benzos, cycle drugs, do not use it for prolonged time.
 
There is also the fact that not all cannabinoids are necessarily selective for cannabinoid receptors.. and not much study has been done on affinities for other receptors especially for most of them which have no studies.. ha. For example, CBD from cannabis is also a 5ht1a agonist and something of a opoid receptor modulator and that is one straight from the plant.
 
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