Cannabis has been used as a medicine for thousands of years by everyone from the ancient Romans, Greeks, and Egyptians; to Indians, Assyrians, and the ancient Arab world more generally. Whilst these ancient cultures were obviously aware of the therapeutic potential of cannabis, they existed before the dawn of modern science, and so obviously could not have had any real understanding of what it was about cannabis that helped them.
Nowadays, we are learning more and more all the time about what cannabinoids are, how they work, and the potential benefits and down-sides of their use as medicine. Interestingly, we have got to this point by taking our cues from ancient civilisations. For example, a folk story of an Arab leader who suffered from epilepsy and was cured by cannabis prompted early cannabinoid researchers to carry out experiments on people with epilepsy, to see whether cannabis could indeed help them.
Those early researchers, most notably Professor Raphael Mechoulam, drew on ancient knowledge to kick-start a proper scientific understanding of cannabis and cannabinoids which continues to expand and develop to this day. What follows is a brief timeline of possibly the most important studies undertaken into cannabinoids since Professor Mechoulam first isolated THC.
1964 – ‘Isolation, Structure, and Partial Synthesis of an Active Constituent of Hashish’
Delta-9-Tetrahydrocannabinol is first isolated, and its structure examined, by Professor Raphael Mechoulam and Dr Yechiel Gaoni at the Weizmann Institute of Science, Israel. According to Professor Mechoulam, the hashish he and his team used was obtained from the police, at first illegally and without the correct permits. Luckily he was not punished for this, as this discovery marks the beginning of modern cannabinoid research.
1980 – ‘Chronic administration of cannabidiol to healthy volunteers and epileptic patients’
Undertaken by Professor Mechoulam and his team, this is the study that drew on the old Arabian story of the leader who was cured of his epilepsy by taking cannabis. It was admittedly only a small study, but it is still the only clinical trial conducted on humans into the effectiveness of CBD as a treatment for epilepsy. Out of 8 patients involved in the trial, 4 remained almost or completely seizure free, 3 saw some improvement, and 1 saw no effect. No dangerous side-effects were noted.
1986 – ‘Cannabinoids as Therapeutic Agents’
Edited by Professor Mechoulam, this important work pulled together the known research into cannabinoid science at the time and posed an important question – “Are we missing something?”
At this point, the scientific world had still only studied the effects of phyto-cannabinoids (from the cannabis plant), and had not yet worked out how or why they produced the effects that they did, or whether there was an endogenous version of these molecules at work within the human body. This was soon to change…
1990 – ‘Stereochemical effects of 11-OH-Δ8-tetrahydrocannabinol-dimethylheptyl to inhibit adenylate cyclase and bind to the cannabinoid receptor’
Professor Allyn Howlett et al discover, for the first time, CB1 receptors in humans. This momentous discovery showed the system in the human body which cannabinoids act upon, and triggered a race to discover endogenous cannabinoids which act on the same system, since it could not be the case that humans (and all mammals as it transpired) have a biological system designed to be triggered only by molecules found in cannabis, outside of the human body. This partly answered the question of ‘are we missing something?’, but not fully.
1992 – ‘Isolation and structure of a brain constituent that binds to the cannabinoid receptor’
Mechoulam, Lumir Hanus, Roger Pertwee, Bill Devane, and others discover Anandamide, the first known endogenous cannabinoid. After years of trying, and worries about being beaten to it by other labs, Anandamide was finally discovered by Bill Devane. At the beginning of their search Raphael Mechoulam had told Devane that if he discovered the endogenous cannabinoid, he would get to name it. So rather than sticking with the actual chemical name – Arachidonoyl Ethanolamide – Devane named the molecule Anandamide, after the Sanskrit word Ananda, meaning bliss or happiness. Six years after Mechoulam first asked the question, scientists finally knew what we had been missing.
1993 – ‘Molecular characterization of a peripheral receptor for cannabinoids’
The discovery of CB2 receptors. A group of scientists from Cambridge discovered a second type of cannabinoid receptor which, unlike CB1 receptors, is found throughout the body rather than being restricted to the brain. The discovery of this receptor helped provide a molecular explanation of the established effects of cannabinoids on the immune system, which had previously been a mystery.
1995 – ‘An efficient new cannabinoid antiemetic in pediatric oncology’
Raphael Mechoulam & Aya Abrahamov decided to test the anti-nausea (antiemetic) effects of cannabis, which had been documented throughout history but never scientifically tested, on children undergoing treatment for cancer. The side-effects of such treatment include severe nausea and are often hugely traumatic for anyone receiving the treatment, but especially so in children. The study was initially a double-blind study, with a control group of children who were not receiving THC along with their cancer treatment. After one week however, it was decided that it was so obvious which children were receiving THC, and the effect it was having on them was so positive, that they began administering it to all of the children in the study. They found that 2-3 doses per day stopped nausea completely, and without any psychoactive effects.
2004 – ‘Amyotrophic lateral sclerosis: delayed disease progression in mice by treatment with a cannabinoid’
Amyotrophic Lateral Sclerosis, more often known in the UK as Motor Neurone Disease, is an incurable disease which always takes the life of its victim, and for which the treatment options available are severely limited. It must be stressed that this study was carried out on mice, and is in no way suggestive of a cure for ALS, but the results were promising. Mice which received THC lived longer and fared better than those which did not, due to THC’s neuroprotective qualities.
2005 – ‘Prevention of Alzheimer’s disease pathology by cannabinoids: neuroprotection mediated by blockade of microglial activation’
Anecdotal evidence has long existed regarding cannabis’ effects on people suffering from Alzheimer’s disease. This study, whilst only a first step on the path to fully understanding the relationship between the two, provides strong enough evidence to offer real hope that cannabis and cannabinoids could, in time, help us to combat a disease which is reaching epidemic levels across the world, which will only continue to rise as the population ages.
2006 – ‘A pilot clinical study of Δ9-tetrahydrocannabinol in patients with recurrent glioblastoma multiforme’
Whilst it has been long-established that THC and CBD can both induce apoptosis and cell-death in cancer cells in a test tube, this was the first human trial undertaken to study whether or not THC can be an effective treatment for cancer in the real world. All of the patients involved were suffering from one of the most aggressive and hard to treat forms of cancer – glioblastoma multiforme – and were not expected to survive. The results of the study were mixed, but did suggest that THC can indeed inhibit tumour growth at least temporarily in some patients. As with the Alzheimer’s research, it is very early days and this was a very small study, so despite the many anecdotal stories of cannabis ‘curing’ cancer, the science isn’t there yet. This was a ground breaking study however, and will hopefully pave the way for more clinical trials in the future.
2007 – ‘Cannabinoid receptors and the regulation of bone mass’
Endogenous cannabinoids and CB2 receptors discovered in bones by Professor Itai Bab. This research showed that both the cells which degrade our bones, and the cells which rebuild them, produce Anandamide and express CB2 receptors, suggesting an important role for the endocannabinoid system in regulating bone strength. This is another area, along with Alzheimer’s and similar diseases, in which we must increase our understanding given our ability as a species to live for far longer than our ancestors.
Clearly, there are many hundreds if not thousands of other studies which could be included in this list, but these are in my view the key moments in cannabinoid research so far. Many people will look at some of the claims made by the studies I have chosen and think they are absurd, so I will end with a quote from Professor Mahmoud A. Elsohly. Speaking in a recent documentary about the work of Raphael Mechoulam, he said, in reference to how people scoffed at ancient stories of cannabis’ medical properties:
“[They would say] this is crazy, there is no such plant that can do all of this. And today it’s very easy to really go back to this old literature about the different indications for which marijuana was prescribed and find out that there is justification for that.”
Who knows what discoveries are still to be made, the potential possibilities are mind-blowing.