Studies with the synthetic cannabinoid Marinol in the mid-1980s, a pure synthetic form of THC that was thought to have the same effect as the cannabis plant as a whole, soon showed that most patients did not react the same as when THC was consumed by smoking or ingesting naturally grown cannabis. Researchers quickly realised that other compounds, such as CBD and various terpenes, play a greater role than previously recognised.
In 1998, the concept of the entourage effect was introduced by Israeli scientists Shimon Ben-Shabat and Raphael Mechoulam. The theory is that cannabinoids within the cannabis plant work together through a network of random relationships as part of a larger organism and influence the body in a mechanism similar to the body's own endocannabinoid system. In principle, these connections work better together than in isolation.
Research into the functioning of THC and CBD in isolation is well established. THC has analgesic, anti-emetic and anti-inflammatory properties. CBD has purported anti-psychotic, anti-seizure and anxiety-reducing properties. However, there is increasing evidence that by isolating these cannabinoids or creating them in a lab, the resulting effects can only have limited therapeutic value. Synthetic forms of THC can even have severe life-threatening side effects, such as acute psychosis or cardiac arrest. The long-term, successful use of cannabis as a whole makes it necessary to find a reason for its medicinal superiority compared to products containing isolated, loose components of the cannabis plant, or synthetic cannabinoids attempting to replicate the natural components.
Ingestion of high doses may cause THC overdosage. Although an acute overdose of natural THC rarely requires medical assistance, the side effects can be experienced as being very unpleasant. Good evidence now shows that THC and CBD are working together. CBD is known to block THC at the CB1-receptor. Therefore, the application of the entourage effect, an increase of the CBD content in case of overdose, may reduce the effects of THC
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