Scientists at the University of East Anglia, University of Barcelona, University Pompeu Fabra and several other European institutions have found a way to separate the medical benefits of cannabis from some of its unwanted side effects.
The research comes from the team that had previously discovered how the main psychoactive ingredient in cannabis, known as tetrahydrocannabinol or THC, reduces tumour growth in cancer patients.
Their latest findings, publishing on July 9th in the Open Access journal PLOS Biology, reveal how some detrimental cognitive effects of THC are triggered by a pathway which is separate from some of its other effects.
That pathway involves both a cannabinoid receptor and a serotonin receptor. When it is blocked, THC can still exert several beneficial effects - including pain relief - while avoiding impairment of memory.
The research was carried out in mice, but it is hoped that the breakthrough will pave the way for safe cannabis-based therapies that do not cause alterations in mood, perception or memory.
Dr Peter McCormick, from University of East Anglia's school of Pharmacy, said: "THC, the major active component of marijuana, has broad medical use - including for pain relief, nausea and anxiety. Our previous research has also found that it could reduce tumour size in cancer patients. However it is also known to induce numerous undesirable side effects such as memory impairment, anxiety, and dependence. There has been a great deal of medical interest in understanding the molecular mechanisms at work in THC, so that the beneficial effects can be harnessed without the side-effects. THC acts through a family of cell receptors called cannabinoid receptors. Our previous research revealed which of these receptors are responsible for the anti-tumour effects of THC. This new research demonstrates how some of the drug's beneficial effects can be separated from some its unwanted side effects."
The research team carried out behavioural studies in mice and investigated how pathways in their brains operate under THC. They found that the absence of a particular serotonin receptor known as 5HT2AR reduced some of the detrimental cognitive effects of THC - such as amnesia. However, the treatment to reduce 5HT2AR did not change the beneficial effect of THC on pain relief.
"This research is important because it identifies a way to reduce some of what, in medical treatment, are usually thought of as THC's unwanted side effects, while maintaining several important benefits including pain reduction", said Dr McCormick.
However, he warned that patients should not be tempted to self-medicate, "patients should not use cannabis to self-medicate, but I hope that our research will lead to a safe synthetic equivalent being available in the future."
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Citation: Viñals X, Moreno E, Lanfumey L, Cordomí A, Pastor A, de La Torre R, et al. (2015) Cognitive Impairment Induced by Delta9-tetrahydrocannabinol Occurs through Heteromers between Cannabinoid CB1 and Serotonin 5-HT2A Receptors. PLoS Biol 13(7): e1002194. doi:10.1371/journal.pbio.1002194
Funding: This study was supported by grants from the Spanish 'Ministerio de Ciencia e Innovación' (SAF2011-29864) to RM, (SAF2010-18472) to PJM and (SAF2011-23813) to EC. 'Ministerio de Economía y Competitividad' (SAF2014-59648-P) to RM. The Spanish 'Instituto de Salud Carlos III' (P1070709 and PI14/00210) to PR and (RD06/001/001) to RM, the Catalan government (SGR2009- 00131) to RM. PJM was supported by a Ramon y Cajal Fellow and internal funds from UEA, and PJM and LP participate in the European COST Action CM 1207 (GLISTEN). FEDER funds partial support is also acknowledged. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: The authors have declared that no competing interests exist.