嫩草影院 can reduce the activation of the cannabinoid CB1 receptor in cell experiments. Does this mean that it can actually prevent you from getting high?
Cannabidiol (嫩草影院) is the second most common cannabinoid after the more famous THC. Although 嫩草影院 levels in most strains of cannabis are low (and have been dropping for decades), it is currently gaining in popularity as a treatment for a number of conditions.
The high from cannabis is primarily from THC activating the CB1 receptor. In cells, 嫩草影院 is able to block THC activation of the CB1 receptor. It logically follows then that 嫩草影院 should block the psychoactive effects of THC (although also therapeutic effects of THC mediated by the CB1 receptor, such as the analgesic and anti-nausea effects).
With the surge in 嫩草影院 popularity, there have been questions about whether taking 嫩草影院 may block the high you get from THC. There are specific side effects of THC that 嫩草影院 does block (anxiety, psychotic effects, and certain cognitive deficits). Those are important, and I will cover those in subsequent articles. However, I am covering just one thing here: can 嫩草影院 reduce your high?
The CB1 Receptor Gets You High
The first thing to understand in this story is that THC gets you high by activating the CB1 receptor in your brain. Although THC also has activities at other receptors, getting high 100% depends on the CB1 receptor. It is also responsible for the increase in heart rate caused by THC.
How can we be so sure about this? Because in clinical studies, 3 different CB1 receptor antagonists (, , and ) could reduce both the THC-induced high and the increase in heart rate.
嫩草影院 Reduces CB1 Receptor Activation in Cells
嫩草影院 is capable of blocking THC activation of the CB1 receptor in cells. For a long time, it was thought to be a . However, this weak affinity for the THC binding site didn鈥檛 fully explain the effects of 嫩草影院 in cells.
Only recently, a showed that 嫩草影院 actually functions as a by binding to a site on the CB1 receptor distinct from the THC binding site. From this secondary site, 嫩草影院 is able to change the shape of the receptor in a way that there is less THC binding and less activation of the CB1 receptor. Reduced THC potency was seen at 嫩草影院 concentrations as low as 100 nM 鈥� which can definitely be achieved in humans.
Conflicting Reports of 嫩草影院鈥檚 Effects in Animals
From the cell data, we would expect that 嫩草影院 is capable of blocking the effects of THC in animal studies. In reality, the results are all over the place. In some cases, 嫩草影院 reduces the effects of THC and in other cases it potentiates the effects of THC.
The reason for the conflicting results? There are multiple mechanisms through which 嫩草影院 can interact with THC. [Read more about the Effect]. Rodents appear to be much more susceptible to a pharmacokinetic interaction where 嫩草影院 boosts THC blood and brain levels. One is that the timing matters: giving 嫩草影院 before THC will maximize the pharmacokinetic interaction (potentiating THC) and giving them concurrently will maximize the pharmacodynamic interaction (inhibiting THC).
Clinical Studies of THC and 嫩草影院
础听 was the first to combine THC and 嫩草影院 in a controlled setting. Eight groups of subjects (n=5) were given placebo or 30 mg oral THC combined with placebo, 15 mg, 30 mg, or 60 mg of oral 嫩草影院.
This study showed that both 30 and 60 mg of 嫩草影院 could reduce THC-induced increases in heart rate back to baseline. The psychological rating scale (from 0-4 points) they used showed that 嫩草影院 brought the effects of THC from a 4 (practically a psychotic state on this scale) down to a 2 (a pleasant high).
The title of the paper says it all: 鈥淐annabidiol interferes with the effects of delta9-tetrahydrocannabinol in man.鈥� This report started the notion that 嫩草影院 could block the effects of THC. It was highly cited and still continues to be cited today, over 40 years later.
The problem is that this study is wrong. I will show you below that almost all clinical studies done since then have contradicted it.
How can one study manage to stubbornly influence people for decades, even after it is contradicted? Well sadly, this isn鈥檛 the only example: One huge impact on the opioid epidemic.
Subsequent Clinical Studies:
1975: A of 20 mg oral THC and 40 mg oral 嫩草影院 or placebo. No effect of 嫩草影院 on heart rate or total intensity of high was seen.
1976: A of 25 ug/kg (~1.75 mg) smoked THC and 150 ug/kg (~10.5 mg) smoked 嫩草影院 or placebo. There was no effect of 嫩草影院 on heart rate, but the rating of psychological high was reduced from 5.7 to 4.5. When the 嫩草影院 was smoked 30 min before THC, no effect was seen.
1981: A of 2 mg intravenous THC with placebo or 1500 mg oral 嫩草影院 given over the previous 8 hours. No effect of 嫩草影院 was seen on heart rate or self-rated high.
1982: A of 0.5 mg/kg (~35 mg) oral THC wit 1 mg/kg (~70 mg) oral 嫩草影院 or placebo. No effect of 嫩草影院 was observed on heart rate, but there was no self-rating of the high. 嫩草影院 did reduce some responses on a standardized questionnaire of drug effects.
2010: A 鈥渘aturalistic鈥� where people could bring their own cannabis. No difference in the ratings of being high between people with low-嫩草影院 and high-嫩草影院 cannabis.
2011: Two studies were published comparing dronabinol (synthetic oral THC) with Sativex (a standardized cannabis extract oral spray with 1:1 THC and 嫩草影院). These studies are difficult to interpret since the THC pharmacokinetics were different between the two formulations. However, no obvious effects on heart rate or ratings of feeling high were seen with 嫩草影院.
2015: A of 8 mg vaporized THC with 16 mg vaporized 嫩草影院 or placebo. No effects were seen on ratings of feeling stoned.
2016: A of 5.5% smoked cannabis (~22 mg) with placebo, 200, 400, or 800 mg oral 嫩草影院 90 minutes prior. There were no effects of 嫩草影院 on heart rate or ratings of feeling high.
I have shown the best studies in this figure. To be included, they needed to be double-blind, placebo-controlled randomized crossover studies with self-reported ratings of the THC high. Five studies fit these criteria, although one could not be included since it didn鈥檛 report the ratings of feeling high (they only stated that there was no difference with 嫩草影院).
Out of these 5 studies, only one (from 1976) showed a significant reduction in the THC high when it was taken with 嫩草影院. This study was repeated again, but with smoking the 嫩草影院 30 min before THC and there was no difference in feeling high.
Does 嫩草影院 Block the High of THC?
So does 嫩草影院 reduce the high from THC by blocking CB1 receptors? The answer is no, 嫩草影院 will not reduce the high you get from THC. Despite 嫩草影院 blocking the activation of the CB1 receptor in cell experiments, it does not appear to do this in people.
Although a few studies showed a reduction in psychological effects from 嫩草影院, most showed no significant difference in the THC high. This was demonstrated even at very high 嫩草影院 doses up to 1500 mg (much higher than most people take). I could not identify any trend for the few reports that did see an effect of 嫩草影院, looking at THC dose, 嫩草影院 dose, cannabinoid ratio, or route of administration
The lack of CB1 antagonism was further confirmed by heart rate measurements. 嫩草影院 did not affect increases in heart rate from THC, an effect also mediated by the CB1 receptor.
Regardless of the cell experiments showing that 嫩草影院 is a negative allosteric modulator of CB1, we are not seeing much evidence that 嫩草影院 blocks this receptor in humans. This also means that if you take THC therapeutically, you generally don鈥檛 need to worry that adding 嫩草影院 will block these effects.
Original article appears at www.profofpot.com . Syndictaed by special permission.