Marijuana and marijuana products have been used in various religious, recreational and medical preparations for centuries. The main cannabinoid in cannabis is THC which produces behavioral, analgesic, cardiovascular, cognitive and pyschomotor effects in the human body. THC is one of the main psychoactive components found in cannabis and it effects the cannabinoid CB1 receptor which is located primarily in the peripheral and central nervous systems.
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The endocannabinoid system in the human body also has a second receptor sub-type (CB2) which seems to be concentrated in the peripheral immune system of the body. The development of SR141716, as the first antagonist that targets the CB1 receptor specifically, could lead to improved research on the functions of the endocannabinoid system. SR141716 prevents effects of the cannabinoid agonists in vivo and in vitro as well as causing withdrawal symptoms in animals that have been given THC over an extended period of time.
SR141716 is a CB1 cannabinoid receptor antagonist which was developed fairly recently. This cannabinoid receptor antagonist blocks the acute effects of THC (tetrahydrocannabinol) as well as other CB1 cannabinoid agonists. Tests have been done on animals and in vitro to assess whether this antagonist can mediate the effects of cannabis, but no human testing has been done to date. This article looks specifically at the effects of SR141716 on humans who have a history of cannabis use.
Healthy male subjects with a history of marijuana use were used for the tests. Sixty-three subjects were given doses of 1,3,10,30 and 90mg of SR141716 or a placebo on a random basis. Subjects smoked a placebo marijuana cigarette or an active marijuana cigarette containing 2.64% THC, 2 hours after receiving the SR141716 dose.
Psychological effects were measured before the administration of the SR141716, before smoking the marijuana as well as after smoking the cigarette. The subjects heart rates were also checked at the same time. SR141716 was well tolerated by the subjects and there did not appear to be any psychological or physiological effects from the SR141716 doses.
SR141716 showed a significant blockade of the tachycardia and intoxication usually experienced by the use of cannabis. This was dose dependent with the 90mg dose producing a 38% to 43% reduction based on scale ratings of questions asked to determine how high the person was feeling. There was also a 59% reduction in heart rate. The pharmakinetics of THC were not affected at all. This conclusively confirms the central role of CB1 receptors when it comes to the mediation of the effects of cannabis on the human body.
The findings of this study demonstrated that when treated with the SR141716 CB1 receptor antagonist, there was a significant blockade of the effects of cannabis on the CB1 receptor. SR141716 on its own produced no significant reaction in the subjects. While this study is however far from conclusive and had many limitations including the effect only being around 40% to 75% effective in subjects using the highest dose of SR141716.
The maximum blockade possible against THC’s effects on the CB1 receptor antagonism has not yet been identified which leaves room for possible mediation from other aspects such as the CB2 receptor antagonism.
Further studies would need to be done to determine the maximum blockage. A wider range of subjects would also be useful as well as the tests being done closer to last use of marijuana prior to the study. The study does however offer significant implications for understanding more about the neurobiology of the endocannabinoid system in the human body as well as its role in possible treatments of clinical disorders.