The discovery of cannabinoids has been a long and fascinating journey. It began in 1940 when British chemist Robert S. Cahn reported on the partial structure of cannabinol (CBN), which he later identified as fully formed. Two years later, American chemist Roger Adams made history by discovering cannabidiol (CBD).
This was followed by the development of psychoactive cannabinoids other than Δ9-THC, which revealed that tolerance can develop to many of the effects of cannabis. The breakthrough came with the discovery of cannabinoid receptors, which allowed researchers to establish that the internalization of these receptors with or without their subsequent degradation, the decrease in the synthesis of CB1 receptor proteins and reductions in the efficiency of CB1 receptor signaling (desensitization) may contribute to the development of tolerance to the agonists of these receptors. However, much less is known about tolerance to the CB2 receptor-mediated effects of cannabinoids. In 1992, scientists identified N-arachidonoylethanolamine, the first endogenous cannabinoid neurotransmitter.
This neurotransmitter was given the name “anandamide”, which in Sanskrit means happiness, a word that suggests its mood-altering effects. In 1940, CBN was the first cannabinoid to be isolated and purified from cannabis. It is a very weak psychotropic cannabinoid, whose effect can only be measured after intravenous administration. CBN has important anticonvulsant, sedative and other pharmacological activities that are likely to interact with the effects of THC.
It has been shown to decrease heart rate without affecting coronary blood flow, decrease intestinal motility and inhibit platelet aggregation. In addition, CBN is a downregulator of the nuclear factor kappa, a light chain enhancer of activated B cells (NF-b), thus counteracting the effects of THC. Before individual cannabinoids were isolated and identified, a group of pioneering scientists laid the fundamental basis for these discoveries. They discovered that when the endocannabinoid system doesn't work properly, cannabinoids in plants can take over and provide relief.
CBG (cannabigerol) comes from the cannabinoid acid CBGA, which plays an integral role in the biosynthesis of cannabinoids. Endocannabinoid signaling facilitates the interaction between gut flora and the brain, a process that is increasingly recognized as fundamental to human health. Quantitatively, the plant is characterized by its potency by measuring the level of its most abundant cannabinoids, Δ9-THC and CBD, in its tissues. However, a large number of more than 100 cannabinoids and cannabinoid acids are waiting for researchers to fully clarify them. A common property of all cannabinoid receptor agonists and antagonists currently used as experimental tools is high lipophilicity and low or negligible solubility in water. Among the first pharmacological observations made with individual cannabinoids are those of Loewe (194), who pointed out that THC and sinhexyl, but not CBD, induced catalepsy in mice; that CBN induced catalepsy in mice, but only at high doses that were also lethal; that THC and sinhexyl had a central exciting action; and that THC and sinhexyl produced THC and sinhexyl, but not CBN or CBD.
Thanks to metabolic enzymes, endocannabinoids are produced when they are needed and then degraded after fulfilling their function. My current research is focused on finding out which compounds, in addition to cannabinoids, play an important role in the treatment of various diseases in cannabis. Hanuš is still at the Hebrew University of Jerusalem, in the team of Raphael Mechoulam, the world's leading expert on cannabinoids.