Cannabis has the potential to make a dent in India’s fight against the escalating threat of antibiotic resistance.
Scientists at CSIR-Indian Institute of Integrative Medicine (IIIM), Jammu, have found that phytocannabinoids, a class of compounds found in the cannabis plant, possess some hitherto unexplored antibiotic properties.
Antimicrobial resistance (AMR) is a major health concern worldwide. It refers to when bacteria, viruses, fungi, and parasites no longer respond to medicines used to treat them.
According to Sanghapal D. Sawant, a senior principal scientist at the CSIR-National Chemical Laboratory (NCL), Pune, bacteria have developed certain sophisticated ‘shields’ over many decades to resist the effects of antibiotic medications.
These include the formation of biofilms – thin sheets of bacterial colonies that are more resistant to antibiotics than when separated – and cellular mechanisms called efflux pumps that flush drugs out from cells.
The resulting AMR increases the risk of disease spread, severe illness, and death.
What is India’s AMR burden?
According to one estimate, India reported 2.97 lakh deaths in 2019 that could be attributed to AMR and 10.42 lakh others that could be associated with AMR.
Reports have also flagged the overuse of antibiotics in India, their misuse in animal husbandry, and poor waste disposal for engendering AMR and potentially rendering India the “AMR capital of the world”.
For these reasons, medical researchers are keen to tamp down AMR and find new drugs that fight AMR pathogens.
In the new study, published in the journal ACS Infectious Diseases, IIIM researchers tested the antibacterial properties of tetrahydrocannabidiol (THCBD), a semisynthetic phytocannabinoid, against Staphylococcus aureus, the bacteria responsible for the second most number of deaths due to AMR worldwide.
Need for ‘alternative solutions’
Antibiotics are chemical compounds isolated from one microorganism and used to kill another. They have saved millions of lives since their discovery but are falling short against AMR bacteria.
“S. aureus includes a strain known as MRSA, for methicillin-resistant S. aureus, resistant to the last line of antibiotics called methicillin,” Parvinder Pal Singh, principal scientist at IIIM researcher and the study’s corresponding author, said. “While numerous antibiotics exist for S. aureus, the emergence of the MRSA strain necessitates alternative solutions.”
The study revealed THCBD obtained from cannabis could fight MRSA. “We tested this molecule on eight to ten different resistant strains of S. aureus, indicating its potential through a distinct mechanism, and offering a promising avenue for further investigation.”
How is THCBD made?
Cannabinoids are a class of compounds found in the cannabis plant. The prefix ‘phyto’ in phytocannabinoid means it comes from a plant. Cannabinoids bind to receptors in the bodies of animals to produce a variety of neurological effects.
The researchers extracted cannabidiol from a cannabis plant and made it react with hydrogen, using palladium as a catalyst. This process yielded a mixture of molecules with the same composition and order of atoms but different structures. One of them was THCBD.
What were THCBD’s effects?
Then the researchers tested THCBD against bacterial cultures in the lab. The minimum quantity found to be efficacious against a strain of Gram-positive S. aureus used commonly in AMR research was found to be 0.25 μg/ml, which the researchers called “potent”.
They found THCBD “demonstrated strong effectiveness” against efflux pump overexpression and MRSA strains.
They also wrote THCBD “significantly reduced” the number of viable microbial cells of S. aureus skin infections in mice.
Finally, they found that the compound either complemented or was indifferent to the effects of other common antibiotics like mupirocin, penicillin G, and ciprofloxacin, meaning they could be used together.
“While we have identified a promising candidate, the journey to transforming it into a viable drug involves overcoming additional hurdles,” Dr Singh said. “The establishment of a comprehensive safety profile is a crucial step that remains to be seen. Moving forward, our focus will include addressing these issues to develop an improved and safer molecule for potential drug applications.”
Is THCBD well-studied?
Nonetheless, Showkat Rashid, a senior scientist at the Medicinal Chemistry Division of IIIM, called the study “very exciting” and “thought-provoking”.
“On one hand, it is well aligned towards the development of new therapeutics against AMR and on the other, it brings the less explored but highly potent phytocannabinoids into the fold” of AMR research.
The main reason it wasn’t in the fold already? THCBD comes from cannabis, which is notorious for its intoxicating properties. As a result it hasn’t been easy to collaborate on phytocannabinoid research with other institutes.
Dr Sawant said research related to cannabis comes up against legal constraints and the need to adhere to specific regulations when studying this plant.
For example, Section 20 of the Narcotic Drugs and Psychotropic Substances Act 1985 restricts the use of cannabis and doesn’t make exceptions for research.
“This research group has been involved in research on cannabis or phytocannabinoids for the past few years. They have devised different strategies and multi-pronged approaches to come-up with potent cannabinoid-based molecules for different disease areas, including cancer, pain management, epilepsy and infections,” Dr Rashid said.
What next for THCBD?
Pankaj Singh Cham, lead author of the study, said the group is “eager to explore collaborations to speed up our progress.”
“Establishing a framework and transportation agreement is important. Currently, many universities lack approval to conduct research on the plant, and efforts are underway to secure government authorisation,” he added.
“The study recently published by Dr Singh’s research group … has presented a unique set of molecules that could be a game-changer in tackling AMR-related problems,” Dr Sawant said. “It is found to have the ability to be a good preclinical candidate, which needs further fine-tuning as far as its drug likeness is concerned.”
He added that addressing the solubility challenge of THCBD could be a “viable strategy”, in addition to conducting a comprehensive safety profile assessment, to pave the way for its use as a drug.
What is the solubility challenge?
Solubility is an important consideration for a drug. For example, many antibiotics are administered orally. Before their active ingredients can be absorbed at a specific site in the body, the drug will need to dissolve in an aqueous solution. If it doesn’t dissolve properly, the body won’t be able to absorb it as intended.
Among other things, solubility is influenced by the properties of the solvent. For example, a molecule can be too hydrophilic (water-loving) or lipophilic (fat-loving), Dr Singh explained. In a biological system, the cytoplasm – which fills the inside of a cell – is a gelatinous liquid and the cell’s wall is primarily composed of lipids.
A drug molecule in this milieu should be neither too hydrophilic nor too lipophilic but in between. THCBD “leans slightly towards lipophilicity”, according to Dr Singh. Achieving this “drug-like” balance is crucial for it to be appropriately soluble.
“In our upcoming efforts, we aim to enhance these properties,” he said.
These studies “could culminate in some fruitful outcome of research and will be useful for society as well,” Dr Sawant added.
Hirra Azmat is a freelance journalist based in Jammu & Kashmir.