A new review of the science around the components of marijuana says the “complex interaction between phytocannabinoids and biological systems offers hope for novel treatment approaches,” laying the groundwork for a new era of innovation in cannabis-based medicines.
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Among other takeaways, the report, published earlier this month in the International Journal of Molecular Sciences, underscores the potential of whole-plant cannabis medicine—incorporating the variety of cannabinoids, terpenes and other compounds produced by the cannabis plant—rather than simply THC or CBD on their own.
“The plant Cannabis exhibits an effect called the ‘entourage effect’, in which the combined actions of terpenes and phytocannabinoids results in effects that exceed the sum of their separate contributions,” the study says. “This synergy emphasizes how important it is to consider the entire plant when utilizing cannabinoids medicinally as opposed to just concentrating on individual cannabinoids.”
Much of the 23-page report—from pharmacy researchers at Ovidus University of Constanta and the University of Medicine, Pharmacy Science and Technology of Târgu Mures, both of which are in Romania—comprises an overview of cannabinoids, including THC and CBD as well as cannabigerol (CBG), cannabichromene (CBC), cannabinol (CBN) and tetrahydrocannabivarin (THC-V)—as well as how those compounds appear to interact with the human body.
While the vast majority of research has studied THC and CBD, the new review notes that the “exploration of novel phytocannabinoids is rapidly evolving, offering exciting prospects for future therapeutic applications.”
“Beyond well-established compounds like THC and CBD, the quest for novel cannabinoids widens the scope of potential treatments,” it says. “Each cannabinoid, with its unique chemical structure, interacts differently with the [endocannabinoid system], suggesting tailored therapeutic effects for specific conditions. This exploration seeks to harness similar benefits while circumventing associated drawbacks.”
Each of the chemical components has specific effects, which the study briefly describes. The broad review, which cites nearly 100 other sources, acknowledges that some effects are bolstered by robust scientific evidence, while others are still being explored.
THC, for example, has demonstrated analgesic effects, authors wrote. “It also possesses antiemetic effects, which make it useful for chemotherapy-induced nausea and vomiting.”
CBD, meanwhile, has demonstrated anti-inflammatory properties and “is said to have analgesic properties and may be effective in pain management.” Some research also shows the cannabinoid may have neuroprotective qualities.
While CBD formulations like the prescription drug Epidiolex can treat rare forms of epilepsy, mixes of CBD and THC may help address spasticity related to multiple sclerosis, the paper says.
Both THC and CBD also have antioxidant effects, it adds, and both appear to be promising tools for a variety of ailments, from pain to neurological disorders and psychiatric conditions.
Further, CBD may help reduce symptoms of anxiety and PTSD, while both THC and CBD may exhibit antidepressant effects. “While some findings suggest that cannabinoids may have mood-stabilizing effects and enhance serotonin signaling, the evidence is inconclusive, and further research is needed,” the study says.
CBD may also help reduce cravings and withdrawal symptoms of alcohol and opioid use disorders, although authors said “the evidence is preliminary, and more research is needed to establish its efficacy and safety.”
Both THC and CBD have also been investigated as possible sleep aids, though results are still preliminary and so far are mixed, with some patients experiencing improved sleep quality while others experience sleep disruptions.
As for treating cancer, the report says that studies have indicated that “cannabinoids can exert antitumor effects directly by inhibiting cell proliferation and inducing apoptosis, or indirectly by inhibiting angiogenesis, invasion, and metastasis.”
“In vivo and in vitro research has demonstrated the efficacy of cannabinoids in modulating tumor growth, although the antitumor effects can vary depending on the type of cancer and the concentration of the drug,” it continues. “For cancer patients, it is crucial to comprehend how cannabinoids control immune system interactions and other biological processes related to carcinogenesis, such as cell cycle progression, proliferation, and cell death. Additional research is necessary for this area.”
As for minor cannabinoids, compounds such as CBG and CBN appear to have antibacterial effects, researchers found. CBN itself also appears to be a mild sedative, which could be relevant for treating sleep disorders.
THC-V, meanwhile, may act as an appetite suppressant and a “potential treatment for diabetes.”
Cannabinoids may also be helpful in treating trauma wounds, authors noted, potentially reducing perceived pain, inflammation and secondary tissue damage.
“At the site of injury, cannabinoids may decrease the release of tissue activators and sensitizers, modulating nerve cells to control tissue destruction and immune cells to prevent the release of proinflammatory substances,” they wrote. “This modulation helps minimize pain and temper post-injury responses associated with inflammatory injury.”
The review also assesses the “challenges and controversies” surrounding research and use of therapeutic cannabinoids, including legal and regulatory obstacles that still vary widely across the globe, a lack of robust standardization of cannabinoid products and the potential for abuse and dependence.
THC, researchers acknowledge, is not only the primary psychoactive compound in cannabis but also the most common cannabinoid associated with problem use. “While the overall risk of addiction to THC is lower compared to substances like opioids, amphetamines, or alcohol,” authors wrote, “it is still a concern, particularly for individuals who use cannabis frequently or in high doses.”
On the other hand, CBD “is not associated with the same potential for abuse or dependence” and “may even have potential therapeutic effects in reducing addiction to other substances, such as opioids, alcohol, or nicotine.”
Social and legal obstacles, the study noted, still make research onerous.
“Despite its potential, legal restrictions and societal stigma surrounding cannabis hinder investment in research and development,” authors of the study wrote. “Complex regulatory frameworks further complicate exploration efforts. Rigorous preclinical and clinical trials are imperative to establish safety and efficacy before therapeutic implementation.”
As cannabinoids and the body’s own endocannabinoid system continue to be better understood, the researchers expect even more “potential in managing various pathological diseases.”
“Phytocannabinoids offer diverse therapeutic applications, ranging from pain management to neurological disorders and inflammatory diseases. Their antimicrobial and anti-inflammatory properties make them valuable candidates for combating antibiotic resistance and modulating inflammatory pathways,” the study concludes. “By leveraging the synergistic effects of combination therapies and targeting multiple disease pathways, phytocannabinoids hold immense potential to revolutionize the future of pharmacotherapy and improve human health outcomes.”
The new research is part of a growing field of investigation into the entourage effect in cannabis as well as in entheogenic plants and fungi. While Western medicine typically seeks to identify and isolate a single active ingredient, the findings underscore the potentially powerful interactions of various chemical components produced by the plant.
Earlier this year, for example, a study looked at the “collaborative interactions” between cannabinoids, terpenes, flavonoids and other molecules in the plant, concluding that a better understanding of the relationships of various chemical components “is crucial for unraveling cannabis’s complete therapeutic potential.”
Other recent research funded by the National Institute on Drug Abuse (NIDA) found that a citrusy-smelling terpene in marijuana, D-limonene, could help ease anxiety and paranoia associated with THC. Researchers similarly said the finding could help unlock the maximum therapeutic benefit of THC.
A separate study last year found that cannabis products with a more diverse array of natural cannabinoids produced stronger psychoactive experiences in adults, which also lasted longer than the high generated by pure THC.
And a 2018 study found that patients suffering from epilepsy experience better health outcomes—with fewer adverse side effects—when they use plant-based CBD extracts compared to “purified” CBD products.
Scientist last year also discovered “previously unidentified cannabis compounds” called flavorants that they believe are responsible for the unique aromas of different varieties of marijuana. Previously, many had thought terpenes alone were responsible for various smells produced by the plant.
Similar phenomena are also beginning to be recorded around psychedelic plants and fungi. In March, for example, researchers published findings showing that use of full-spectrum psychedelic mushroom extract had a more powerful effect than chemically synthesized psilocybin alone. They said the findings imply that mushrooms, like cannabis, demonstrate an entourage effect.
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