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A peptide that allows cannabis-derived drugs to relieve pain without side effects

Scientists from the Proteomics and Protein Chemistry Research Group and the Neuropharmacology-Neurophar Laboratory have developed a peptide which is an ideal candidate for reducing the cognitive side effects of pain treatment with cannabis derivatives.

A peptide that allows cannabis-derived drugs to relieve pain without side effects
2021-05-20
(Press-News.org) An international team, led by researchers from Pompeu Fabra University (UPF) in Barcelona, Spain, David Andreu and Rafael Maldonado, has developed a peptides family that allows delta-9-tetrahydrocannabinol (THC), the main component of Cannabis sativa, to fight pain in mice without side effects. The study, published in the Journal of Medicinal Chemistry, was carried out together with researchers from the Autonomous University of Barcelona, ??the University of Barcelona, and the University of Lisbon.

At present, there are two main types of pain relievers prescribed based on the severity of the pain. Nonsteroidal anti-inflammatory drugs (NSAIDs, such as ibuprofen or paracetamol) are often used to treat mild pain, while opioids are used for severe pain. These, although effective, have significant addictive potential. A therapeutic window is not covered between these extremes, as there is a lack of safe and effective drugs to treat moderate chronic or neuropathic pain (such as that caused by nerve damage for people with diabetes or herpes). In this scenario, cannabis-derived drugs have an excellent opportunity to provide relief, but their therapeutic use is limited by their side effects, including problems with memory and other cognitive functions.

THC produces analgesia by binding to cannabinoid type 1 (CB1) receptors. However, these receptors interact with the serotonin receptor 5HT2A, and this interaction causes memory loss when THC is present. To address this problem, the interaction between the two receptors must be avoided. That is why scientists from the Proteomics and Protein Chemistry Research Group and the Neuropharmacology-Neurophar Laboratory have designed and produced peptides that interrupt the interaction between the two receptors, so the THC can ease pain without activating the serotonin receptor.

In a previous study, when researchers injected a peptide into the brains of mice, the memory problems caused by THC decreased. Based on molecular dynamics simulations and current pharmaceutical chemistry strategies, the researchers have optimized the original prototype by developing a smaller peptide with high stability, allowing oral administration while increasing its ability to cross the blood-brain barrier to access and act on brain cells.

After administering mice with the peptide orally, along with an injection of THC, they assessed pain threshold and memory capacity. Mice treated with both THC and the optimized peptide obtained the benefits of THC in relieving pain and also showed better memory compared to those treated with THC alone. "Our results suggest that the optimized peptide is an ideal candidate for reducing the cognitive side effects of pain treatment with cannabis derivatives," says Rafael Maldonado, Professor of Pharmacology in the Department of Experimental and Health Sciences (DCEXS) at UPF.

"Given the results obtained so far, the team is motivated to advance in the development of this promising candidate discovered," explains David Andreu, UPF Professor of Chemistry.

"The INNOValora programme will allow us to partially cover the proof-of-concept experiment in chronic pain that we need to ensure investors' participation in the project," says Maria Gallo, a PhD student from the Proteomics and Protein Chemistry group at the DCEXS-UPF, whose doctoral thesis recapitulates much of the project's experimental work.

"We envision the use of the peptide in combination with THC as the first drug approved by the EMA / FDA for the treatment of chronic pain," concludes Rafael Maldonado.

These results have been the basis for an international patent application that is expected to be transferred to the pharmaceutical sector once the preclinical and clinical validation experiments required by drug regulations are completed.

INFORMATION:

Funding

The work has been supported by the Marie Sk?odowska-Curie Research and Innovation Staff Exchange Programme, the Spanish Ministry of Economy and Innovation, the La Caixa Foundation and, now, the UPF INNOValora programme.

Reference article

Gallo M et al. Orally Active Peptide Vector Allows Using Cannabis to Fight Pain While Avoiding Side Effects. Journal of Medicinal Chemistry. DOI: 10.1021/acs.jmedchem.1c00484.


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A peptide that allows cannabis-derived drugs to relieve pain without side effects

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[Press-News.org] A peptide that allows cannabis-derived drugs to relieve pain without side effects
Scientists from the Proteomics and Protein Chemistry Research Group and the Neuropharmacology-Neurophar Laboratory have developed a peptide which is an ideal candidate for reducing the cognitive side effects of pain treatment with cannabis derivatives.