How does cannabis work in your system?

By Richard Shrubb

My last blog discussed the endocannabinoid system (ECB). This will tentatively look at how cannabis works when it hits the system, and what medicines may come from research into this.

Weed smokers may have changed the world for the better, and advanced medicine in ways few other recreations could ever do. In the 1960’s, scientists asked the simple question, why does cannabis make you stoned? In doing so they discovered two synaptic proteins which react when cannabis goes into the body.  A synapse is a gap between neurons, through which electrical signals pass as chemical signals. Synaptic proteins send and receive these chemicals. They also discovered chemicals similar to the psychoactive ingredients in cannabis, so named them after cannabis, and mooted an “endocannabinoid system”.

In the last 20 years they discovered something unusual. Unlike most chemicals that pass across the synapse, endocannabinoids pass both ways – most neurotransmitters such as dopamine and serotonin just go in one direction. Professor Val Curran of Imperial College London suggests that “endocannabinoids are a synaptic moderator”. Essentially, it is thought that ECB’s regulate the chemicals that pass between neurons, either reducing or increasing the amount of neurotransmitter chemicals that pass between them. ECB’s are one of the most important parts of your brain and nervous system as they seem to regulate the very chemistry of them.

sativex cannabis tincture

Sativex: Expensive super strength cannabis tincture.

In understanding this, so an explosion of research into ECB’s has occurred. GW Pharmaceuticals, a company loved and loathed by many for its expensive Multiple Sclerosis medication Sativex, is researching six potential medicines for everything from neuropathic pain to diabetes, to schizophrenia.

Professor Maurice Elphick of Queen Mary and Westfield University, suggests that “endocannabinoids evolved in animals very early – perhaps 500 million years ago. Humans have it, but so do very basic animals such as sea squirts.” ECB’s are quite simple – there are only two receptor proteins, the CB1 and CB2 receptors. If you look at the neurotransmitter dopamine for example, there are 5 types of receptors in nerves, with an almost baffling amount of functions.

Dr Paul Morrison of Kings College London says that never mind in the brain, in the body ECB’s regulate “a number of processes – fat metabolism, cell migration, immune function, bone density… To my mind, endometriosis, osteoporosis and diabetes are the most promising targets. The pre-clinical work is very consistent.”

Elphick suggests that the simplicity of the ECB system is a blessing and a curse. The first synthetic drug to use the ECB was a medicine called Rimonabant, used to help people lose weight. Elphick says “this worked very effectively at helping people lose weight but the ECB is also about reward [anandamide, an endocannabinoid, is the “bliss chemical”], so in blocking the endocannabinoids from being received by receptors in the body, people felt suicidal”. In this case, the ECB wasn’t understood well enough and a sledgehammer approach was found to be too blunt an instrument for a system that is so important in the way your body works.

Elphick says that ECB receptors react differently according to what chemicals reach a receptor. “This is known in G Proteins throughout the body”. G Proteins are often synaptic receivers, and can receive a number of different neurotransmitters, including in the dopamine, glutamate or serotonin amongst others. Talking to him at length he did come round to saying that sometimes two or more chemicals affecting a synapse can have a different effect to one. This applies in all neurotransmitters, as well as the ECB. He says, “this is called alosteric modulation”.

The endocannabinoid system (ECB).

The endocannabinoid system

The “whole weed approach” mooted by fans of cannabis such as the Multidisciplinary Association of Psychedelic Studies involves giving a number of cannabinoids to the synapses, and having a range of different responses. There may well be something in this through alosteric modulation.  Research though will take quite some time. It has taken fifty years to get where we are today and we still have a decade before medicines become widely available that use the ECB.

This is not to say you should be permanently stoned to sort your endocannabinoid system out! Prof Curran explains that “the brain is in homeostasis like a rainforest. If you put something in from the outside, such as a road, then it will compensate to ensure the right balance”. This means you put too much THC into your system and the body will reduce its anandamide levels to compensate – Curran has a piece of research that has yet to be published that suggests exactly that. By messing with your system unnecessarily you could actually do yourself damage – this in a way Peter Hitchens hasn’t heard of yet!

All three scientists here would prefer a medicine that doesn’t involve smoking a joint. This is not to say they are “against” cannabis, they just feel that getting stoned isn’t welcome when you want to get over neuropathic pain, for example. You will want to get over the pain yet still feel motivated enough to have a life beyond the bhong! Morrison says the chief issue faced in cannabinoid research is intoxication: “The challenge is to develop molecules which have an absence of [Central Nervous System] effects.”

That medicine will use endoncannabinoids in some way to treat a variety of illnesses and conditions is a dead cert. The question now is what will pop up in research, and how it will be used? Thanks to the rigour required in medical research, this may take some time. The signs are promising, but it will be a good decade before we can pick up a wide variety of cannabis derived medicines from the pharmacy.

Richard Shrubb

Richard Shrubb is a freelance journalist with a specific interest in medical science and sailing, for more info about Richard, see his web site and you can follow Richard on Twitter #Shrubberz


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