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Delta-9-Tetrahydrocannabinol as a Therapeutic Agent

Delta-9-Tetrahydrocannibol, commonly called THC, was first isolated in 1964 by Gaoni and Mechoulam 1. It is a phytocannabinoid that binds to both CB1 and CB2 receptors in mammals, with a higher affinity for the CB1 receptors present in our central nervous system. Binding to CB1 receptors is responsible for its trademarked psychoactive properties, and it is believed to be the most psychoactive component of Cannabis sativa 2.


THC has a wide range of therapeutic applications due to its complex and diverse mechanisms of action. These range from acting on opioid and benzodiazepine receptors, prostaglandin synthesis, protein and nucleic acid metabolism, as well as having effects on enzyme systems, hormone secretion and neurotransmitters 4. Due to this diverse range effects medicinal cannabis consumers report using it to help with “pain, spasticity associated with multiple sclerosis, nausea, posttraumatic stress disorder, cancer, epilepsy, cachexia, glaucoma, HIV/AIDS, and degenerative neurological conditions” 5.


Chronic Pain is the most common condition for which medical cannabis is used. A study in 2014 reported that 94% of Colorado medical cannabis ID cardholders indicated severe pain as a medical condition for which they consumed cannabis 6. Another study from 2016 reported that medical cannabis use in pain patients was associated with a 64% reduction in opioid use 7, this is relevant to society today as there is an increasing opioid addiction problem in western countries.


A trial of different strengths of cannabis, performed in 2007, showed that a medium dose of cannabis resulted in a significant decrease in pain, interestingly a high dose was associated with an increase in pain 8. In 2015 a systematic review of 28 randomised trials among 2454 patients showed that, compared to a placebo, cannabinoids (including THC) were associated with a greater reduction in pain and lower numerical pain scores 9.


Chemotherapy-Induced Nausea and Vomiting affects most cancer patients who have chosen to undergo chemotherapy. It is also one of the more frequently reported reasons for medical cannabis use. A host of studies have been performed on the efficacy of cannabis and THC as an anti-emetic, and two THC like drugs Nabilone and Dronabinol have been used for 30 years to help prevent nausea and vomiting 10. Both drugs were found to be superior to the placebo and equivalent to the available antiemetics, this has been demonstrated in many studies over the years 11 & 12.


Despite the well reported usage of THC containing cannabis for preventing nausea it is commonly noted in most studies that they do not exceed the effectivity of prescribed anti-emetics, and are usually only recommended for patients for whom regular anti-emetic medication does not work or is intolerable.


Anorexia Nervosa, HIV/AIDS Wasting Syndrome and Cancer-Associated Anorexia are debilitating diseases that are characterised by unhealthy weight loss. Cannabis sativa has an effect that many consumers refer to as ‘the munchies’ whereby the consumer will eat more than usual, usual between meals in the form of snacking. This has lead to cannabis and THC being explored for its orexigenic (appetite stimulating) effects.


Reference #9 is a comprehensive meta-analysis and review of cannabinoids for medical use. Within this review they highlight several studies that showed THC, and man made varieties like dronabinol, showed some evidence for being able to increase weight in patients affected by these diseases, however the evidence is not as strong as many of the authors expected. The in vitro (in lab) studies on cell cultures and in vivo (in life) studies on animals showcase THC and other cannabinoids being strongly tied to appetite stimulation, so it is strange that these results are not easily replicable in human studies 13. It is believed that other compounds within the cannabis plant may be more responsible for appetite stimulation, or a combination of many of the compounds alongside THC may be the most stimulatory. Moreover, the need for more studies in this area is vitally needed, as most of the findings relating to appetite and anorexic syndromes are merely secondary observations that arise whilst studying other aspects of cannabinoids or the diseases.


Multiple Sclerosis affects roughly 2.5 million people across the globe. A study of 521 MS patients reported 39.9% had used cannabis in some form or another to help them with their symptoms 14. There are however many uncertainties about the positive and negative effects of cannabis use in these patients. There is proof that THC can have positive effects on muscle spasticity and pain when equal levels of CBD are present in the consumed cannabis 15 & 16. The results showed that for the Visual Analogue Scale assessment of symptoms that the cannabis based medicine improved the MS patients’ scores by 34% when administered with Sativex (2.7mg of THC and 2.5mg of CBD per dose). However, other studies produced less noticeable improvements for MS patients.


Tourette Syndrome is a neurological disorder characterised with sporadic movements or vocalizations referred to as “tics”. An understudied area of cannabis medicine, there are two good-quality reviews that looked into the research 9 & 17. No clear link has been established. However, case reports suggest that any reduction in tics may be due to the cannabis and its THC and CBD compounds reducing anxiety and not acting in a tic-specific mechanism 18.


Cancer is thought to occur in 50% of the population at some point in their lives. Much has been made of cannabis and the compounds within it being anti-cancer. But these effects are mainly demonstrated in cell cultures and are hard to replicate in the human body. A wealth of studies performed on cell cultures demonstrate anti-tumour activities of THC but only one clinical trial has been undertaken on the anti-tumour effects of THC within the human body 19. The 9 patients underwent intracranial THC administration to attempt to treat their recurrent glioblastomas. The results showed that some patients partially responded to the treatment and a decrease in tumour growth was observed. Far more study is needed in order to determine if THC truly has any anti-cancer properties in human cancer patients.


Parkinson’s Disease is one of the neurological disorders that cannabis has been thought to have helpful applications for. Anecdotal evidence has been spread on social media that show PD sufferers alleviating their tremors via cannabis based therapies (vaping or smoking of cannabis). However, the scientific studies pertaining to THC’s therapeutic efficacy are lacking. One pilot study showed how Nabilone (a synthetic THC analogue) reduce the involuntary tremors of PD patients 20. More studies are needed to explore this potentially life changing therapy as current studies are very limited and have very few patients.


The efficacy of THC for many ailments and diseases is still under scrutiny. Anecdotal evidence far outweighs the scientific research into the matter and there must be a concerted effort to perform more studies in vivo to accurately determine the anecdotal myths from facts.



References:

1: https://pubs.acs.org/doi/abs/10.1021/ja01062a046

2: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3570572/

3: https://pubmed.ncbi.nlm.nih.gov/12648025/

4: https://pubmed.ncbi.nlm.nih.gov/16596770/

5: https://www.ncbi.nlm.nih.gov/books/NBK425767/

6:https://www.colorado.gov/pacific/sites/default/files/Market%20Size%20and%20Demand%20Study,%20July%209,%202014%5B1%5D.pdf

7: https://pubmed.ncbi.nlm.nih.gov/27001005/

8: https://pubmed.ncbi.nlm.nih.gov/18073554/

9: https://pubmed.ncbi.nlm.nih.gov/26103030/

10: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3442177/

11: https://pubmed.ncbi.nlm.nih.gov/11440936/

12: https://pubmed.ncbi.nlm.nih.gov/6318262/

13: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3150924/

14: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6489434/

15: https://pubmed.ncbi.nlm.nih.gov/16186518/

16: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5481305/

17: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4011465/

18: https://pubmed.ncbi.nlm.nih.gov/22291003/

19: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360617/

20: https://pubmed.ncbi.nlm.nih.gov/11739835/

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