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Cannabis will not leave us in pain: one third of chronic patients wants it since receptors are not the only target

In various European countries and North America, medical cannabis or medicines based on cannabinoids are authorized for therapeutic purposes. As more american states legalize cannabis for medical and recreational use, increasing numbers of people are experimenting with it for pain relief. According to a new study published in JAMA Network Open, almost a third of patients with chronic pain reported using cannabis to manage it. More than half of the 1,724 adults surveyed reported that using cannabis led them to decrease the use of pain medications, including prescription opioids and over-the-counter analgesics. Cannabis also effected the use of other non-drug related pain relief methods to various degrees: some people indicated that cannabis led them to turn less often to techniques that many clinical guidelines recommend as first-line therapies such as physical therapy and cognitive behavioral therapy, while others with chronic pain increased their use of such treatments.

While the cannabis plant contains over 100 cannabinoids, THC (D9-tetrahydrocannabinol) and CBD (cannabidiol) are the two best-known and characterized active molecules. THC and CBD are administered under different pharmaceutical forms, showing therapeutic effects such as pain and inflammation relief. Based on clinical trials, cannabinoid-containing medications can help to alleviate symptoms of mental disorders such as epilepsy, Alzheimer’s disease, asthma and help prevent weight loss during clinically challenging treatments for AIDS and different forms of cancer. However, how THC and other cannabinoids work in the human body at the molecular level is not completely understood. The main known targets of THC in the human body are indeed the CB1 and CB2 cannabinoid receptors, that mediate the psychoactive and pain relieve effects of cannabis and endogenous cannabinoids. Therefore, understanding the interactions of cannabinoids in our cells at the atomic level is na hot topic in basic science.

The field of structural biology is particularly relevant to obtain this kind of information. Structural biologists focus on elucidating at the atomic scale the three-dimensional structure of proteins or enzymes, and how they interact with each other. These structural results further lead to understanding molecules’ particular function and how to modulate their activities with specific compounds – which are crucial insights to develop effective drugs. The first step in structural and biochemical studies is to determine how a specific component interacts with molecules in vitro before going for further investigation in vivo, in living organisms. Grenoble EMBL researchers have investigated the interaction between THC and some proteins it might bind to. During their investigation of THC, scientists obtained the 3D structure of THC bound with autotaxin, an important human enzyme. Autotaxin is involved in many different cellular functions, specifically producing a molecule called lysophosphatidic acid (LPA), which stimulates cell proliferation.

A dysregulation of LPA production can lead to development of cancer, inflammation, or pulmonary fibrosis. LPA is involved in inflammation stimulated by ultraviolet radiation in skin and in several conditions where inflammation develops, like traumas, granulomas and even the common osteoarthritis. Autotaxin is therefore a major target for drug development. Identifying this enzyme as a binding target for THC on one side enalrges the explanation of pain-relieving activity; on the other hand, it provides more data on its possible therapeutic effects at the molecular level and how medical cannabis might contribute to therapy. In vivo studies are necessary to confirm that the binding between autotaxin and THC is linked to the therapeutic effects of THC administration. Further investigation will help determine further potential of cannabinoids for medical research and drug development.

  • Edited by Dr. Gisnfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.

Scientific references

Eymery MC et al. Life Sci Alliance. 2023 Jan 9; 6(2):e202201595.

Roy S et al. ACS Chem Neurosci. 2022 Oct 5; 13(19):2829-2841.

Boi R, Ebefors K, Henricsson M et al. Sci Rep. 2022; 12(1):7322.

Bicket MC et al. JAMA Network Open 2023 Jan 3; 6(1):e2249797.

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Dott. Gianfrancesco Cormaci

Medico Chirurgo, Specialista; PhD. a CoFood s.r.l.
- Laurea in Medicina e Chirurgia nel 1998 (MD Degree in 1998) - Specialista in Biochimica Clinica nel 2002 (Clinical Biochemistry residency in 2002) - Dottorato in Neurobiologia nel 2006 (Neurobiology PhD in 2006) - Ha soggiornato negli Stati Uniti, Baltimora (MD) come ricercatore alle dipendenze del National Institute on Drug Abuse (NIDA/NIH) e poi alla Johns Hopkins University, dal 2004 al 2008. - Dal 2009 si occupa di Medicina personalizzata. - Guardia medica presso strutture private dal 2010 - Detentore di due brevetti sulla preparazione di prodotti gluten-free a partire da regolare farina di frumento enzimaticamente neutralizzata (owner of patents concerning the production of bakery gluten-free products, starting from regular wheat flour). - Responsabile del reparto Ricerca e Sviluppo per la società CoFood s.r.l. (Leader of the R&D for the partnership CoFood s.r.l.) - Autore di articoli su informazione medica e salute sul sito www.medicomunicare.it (Medical/health information on website) - Autore di corsi ECM FAD pubblicizzati sul sito www.salutesicilia.it
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