IN CONTRAST TO THAT INFERRED BY SOME TWEETS
Pryce G, Baker D. Antidote to cannabinoid intoxication: Inverse cannabinoid receptor one (CB1) agonism by N-(Piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamidse (AM251) reverses the hypothermic effects of cannabinoid receptor one agonism by 1-Naphthalenyl [4-(pentyloxy)-1-naphthalenyl] methanone (CB13) in mice.
Br J Pharmacol. 2017 Aug 11. doi: 10.1111/bph.13973. [Epub ahead of print]
BACKGROUND & PURPOSE:Cannabis is a recreational drug leading to intoxication, due to cannabinoid receptor one (CB1 ) stimulation. However, more recently herbs mixed with synthetic cannabinoids sometimes known as “Spice” and “Black Mamba” have been increasing used and their high CB1 receptor affinity means not only marked intoxication, but life-threatening complications and an increasing number of deaths. Whilst many studies have indicated that prophylactic CB1 receptor antagonism can block cannabimimetic effects in animals and humans. The aim of the study was to determine whether CB1 antagonism could reverse physical cannabimimetic effects.
EXPERIMENTAL APPROACH: Cannabimimetic effects, measured by the hypothermic response following sedation and hypomotility, were induced by 1-Naphthalenyl[4-(pentyloxy)-1-naphthalenyl] methanone (synthetic CB1 agonist) in Biozzi ABH mice. N-(Piperidin-1-yl)-5-(4-iodophenyl)-1-(2, 4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251. CB1 antagonist/inverse agonist) was subsequently administered and the influence on cannabimimetic effects assessed.
KEY RESULTS: In this study, the pre-existing, central nervous system-related cannabimimetic effects, measured via the hypothermic effect, induced by CB1 receptor agonism where therapeutically treated and were rapidly reversed by CB1 receptor antagonism/inverse agonism. There was also a subjective reversal of visually-evident sedation.
CONCLUSIONS & IMPLICATIONS: Cannabinoid receptor antagonists have been used in thousands of people and so may provide a single-dose antidote to cannabinoid intoxication, which may save human life, if the life-threatening effects are mediated by the cannabinoid receptor and not off-target influences of the synthetic cannabinoids or non-cannabinoids within the recreational drug mixture.
People take cannabis to alleviate symptoms but if you are buying street cannabis you don’t know how much THC is in it and so you may get more than you bargained for. However with cannabis the high isn’t going to kill you.
The synthetic used to change to keep ahead of the law but since last year they are now all illegal in the UK,
The synthetics can get people very intoxicated and there are an increasing number of deaths reported. Now, this could be due to an impurity or non-cannabinoid action, but it could be due to the cannabinoid system such as a seizure or a heart issue as cannabinoids can make your heart race.
Some people think that cannabidiol can do this, but it can only affect the buzz and does not turn the high off.
In this paper we describe a simple experiment that was done a few years ago, when we could legally hold cannabinoids. Now you need a licence costing about 5 grand a year. The use of CB13 as the agonist is not important, it was one that we were researching on at the time, but it could induce a “mouse high”, when we gave the antagonist or should I say “inverse agonist” it turned the “high completely” off within a few minutes so it could act as a antidote.
So may be, if there was a Pot epi-pen people it could be used in peolpe at risk of dying from overdose of “Spice”. If it were available perhaps the 14 year Girl from Bristol who died a few weeks ago may still be here.
There was one inverse agonist that was licenced to treat obesity and it was made by Sanofi…the maker of Alemtuzumab. It blocked cannabinoid receptors in appetite centres in the brain to block the munchies, but it also affected centres controlling depression leading a few people to commit suicide. However, thousands of people have taken the drug (rimonabant) without a problem and if it is a matter of life or death, you’ld risk it. However, sadly Sanofi were not interested, when I asked.
Do I have the energy to develop this, or something like it? Maybe something for Prof. David Nutt (ex UK drug Tsar to the Government) to sink his teeth into. This week we are more busy with our presentations for Roehampton (a London Suburb)….yes the MD’s get to go to the most exotic places to present.
(a) Neuroprotection in an experimental model of multiple sclerosis via fatty acid amide hydrolase or monoacyl glycerol lipase inhibition
(b) Neuroprotection in an experimental model of multiple sclerosis via opening of big conductance, calcium-activated potassium channels.
Do you get the significance of this?