by Micha on 05/02/2016 | Medicinal Opinion

Bliss inhibitors in the human endocannabinoid system

Endocannabinoid On 15 January 2016, numerous media channels reported that in Rennes, France, a participant in a clinical trial died after taking a substance whose effects were supposed to resemble those of cannabis. Read the complete report here.

Bliss inhibitors in the human endocannabinoid system - Sensi Seeds Blog

Clinical trial goes too far

On 15 January 2016, numerous media channels reported that in Rennes, France, a participant in a clinical trial died after taking a substance whose effects were supposed to resemble those of cannabis. While the French Ministry of Social Affairs, Health and Women’s Rights did refute the claim that a cannabis medicine was involved within a few hours, the initial reports were not too far off the mark.

To quote Wikipedia, BIA 10-2474 is an experimental fatty acid amide hydrolase inhibitor, or FAAH. These substances are also known as ‘anandamides’, (a term derived from the Sanskrit word ‘ananda’, meaning ‘bliss’), or ‘FAAH inhibitors’ and they affect the human endocannabinoid system, which is exactly what the cannabinoids in cannabis, such as THC or CBD, do. In this case, however, the incident involved FAAH inhibitors that were made in a laboratory. Because many pharmaceutical companies have promised to develop a large number of FAAH inhibitors and other substances that act on the endocannabinoid system, such as synthetic cannabinoids, research into these substances has skyrocketed in recent years. The objective is, among other things, to fully realise the potential of these substances without “stimulating euphoric states of mind,” as stated by the endocannabinoid specialist Beat Lutz from the University of Zurich in the Frankfurter Allgemeine Zeitung. In addition to avoiding euphoric states of mind, researchers also wish to prevent these substances from being addictive. As such, there are increasing reports of researchers working on cannabis-based medicines that produce no highs. More importantly, however, the substances are simple to develop, can be patented for 10 years following their trial period, and they are unaffected by prejudices and restrictive measures, unlike medicines developed from the cannabis plant itself.

Cause of death still unclear

The study in France therefore did not directly involve cannabis and it had complied with all the regulations set by the EU for Phase 1 tests during clinical trials on humans. The FAAH inhibitor BIA 10-2474, which was developed by the Portuguese company BIAL and was being tested in Rennes by the French company Biotrial, was intended to combat feelings of fear, high blood pressure, chronic pain, obesity and motor problems as a result of Parkinson’s disease. On 15 January 2016, one of the six participants in the clinical trials who, of the more than 90 participants, had received the highest dose of the inhibitor, fell into a coma and died two days later. The other five individuals are in critical condition and three have perhaps suffered irreparable brain damage. The active substance, BIA 10-2474, is a phenylurea that is supposed to influence the human body’s own endocannabinoid system. It is as yet unclear how the death occurred and the French public prosecutor’s office is investigating the incident.  Pharmaceutical company Janssen-Cilag, a subsidiary of Johnson&Johnson, announced soon after the tragedy in Rennes that it would not perform the planned Phase 2 tests with the FAAH inhibitor JNJ-42165279. In the EU, the appetite suppressant Rimonabant, which also affects the endocannabinoid system, was approved in 2006, despite it not receiving approval in the US due to its psychological side effects, such as suicidal thoughts. After the resulting discussion in the EU, Rimonabant’s approval was suspended on the recommendation of the European Medicines Agency and the substance was removed from the market by its manufacturer Sanofi-Aventis.

Wrong priorities

It would of course be wrong to want to limit research into the endocannabinoid system. However, as long as so little is known about the operation of this system, research into and isolation of natural cannabinoids would be a good alternative. Even the discovery of CBD’s plethora of qualities cannot initially be ascribed to the pharmaceutical industry. Instead, it is thanks to the efforts of the private initiatives of many cannabis patients, small businesses and their supporters, which were made possible once the father of research into this cannabinoid, Israeli doctor Raphael Mechoulam, had synthesised this substance. At any rate, the substances in cannabis have thus far not been responsible for any deaths or comas. Nevertheless, the obstacles standing in the way of research, and human trials in particular, are disproportionately larger where natural cannabinoids are concerned than for synthetic cannabinoids and FAAH inhibitors. The knowledge gained by research into natural cannabinoids is difficult to patent and therefore unprofitable, or at least, it is not as profitable as the development of company-specific substances, such as FAAH inhibitors and synthetic cannabinoids. Remember, the supposed addictive properties of natural cannabis serve to benefit the pharma industry; they make it possible to fully focus on the development of private substances for medicinal uses and ignore natural cannabis altogether. Never mind that, in doing so, they are failing to acknowledge 70 natural cannabinoids produced by Mother Nature which, with the exception of THC and CBD, have yet to be seriously studied.

Legal highs as waste product

Incidentally, scientific research into the human body’s endocannabinoid system has given rise to a series of dubious substances in addition to FAAH inhibitors. In the past 20 years, countless THC antagonists have been developed, of which a few have been branded as producing “legal highs”, such as Pfizer’s AB-FUBINACA, instead of being developed into medicines. Today, the list of THC antagonists developed for medical research and development contains more than 160 substances, which is more than is encompassed by the drug legislation in either the EU or US. In addition to the classic THC antagonists, an almost infinite number of so-called non-classical synthetic cannabinoids exists, which are no less psychoactive and which often pose health risks. These substances, which produce “legal highs” and which have been connected to fatal incidents, are growing in number. Rennes is a prime example of the issue: research into natural cannabinoids and their effect on the endocannabinoid system must be made more accessible and intensified as soon as possible. Only then can the medicinal potential of cannabis be utilised to its fullest extent, without human lives being endangered or sacrificed in the pursuit of profits. Moreover, there is an urgent need to more thoroughly investigate the operation of the human body’s cannabinoid system before the next round of bliss inhibitor testing is carried out on humans.

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good one .


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