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<h2 class="element-invisible">You are here</h2><div class="breadcrumb"><a href="/">Home</a> » <a href="/news-events">News & Events</a> » <a href="/news-events/nih-research-matters">NIH Research Matters</a></div> <div class="l-region l-region--section-header">
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<p class="publishdate"><span property="dc:date" datatype="xsd:dateTime" content="2016-11-01T00:00:00-04:00" class="date-display-single">November 1, 2016</span></p><div class='syndicate'><h1>Cannabinoid receptor structure revealed</h1><div class="callout callout-with-border"><h3>At a Glance</h3>
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<li>Scientists provided a detailed view of the primary molecule through which cannabinoids—the active compounds in marijuana—exert their effects on the brain.</li>
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<li>The findings might help guide the design of more targeted medicines with fewer side effects.</li>
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<picture title="CB1 structure">
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<!--[if IE 9]><video style="display: none;"><![endif]-->
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-large/public/news-events/research-matters/2016/20151101-cannabinoid.jpg?itok=fC0ZICdm&timestamp=1478008777 1x" media="screen and (min-width: 960px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium/public/news-events/research-matters/2016/20151101-cannabinoid.jpg?itok=vceQ4Qo_&timestamp=1478008777 1x" media="screen and (min-width: 800px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium-small/public/news-events/research-matters/2016/20151101-cannabinoid.jpg?itok=oIBGkBlX&timestamp=1478008777 1x" media="screen and (min-width: 600px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-small/public/news-events/research-matters/2016/20151101-cannabinoid.jpg?itok=hzKxEZsl&timestamp=1478008777 1x" media="screen and (min-width: 480px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-tiny/public/news-events/research-matters/2016/20151101-cannabinoid.jpg?itok=UFpt2Wlp&timestamp=1478008777 1x" media="screen and (min-width: 0)" />
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<!--[if IE 9]></video><![endif]-->
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<img src="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium/public/news-events/research-matters/2016/20151101-cannabinoid.jpg?itok=vceQ4Qo_&timestamp=1478008777" alt="CB1 structure" title="CB1 structure" />
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||
</picture><span class="caption">The molecular structure of CB1 (yellow ribbon) bound with AM6538 (orange stick structure). THC, the active ingredient in marijuana, is shown as well (yellow stick structures).</span><span class="credit">Yekaterina Kadyshevskaya, Stevens Laboratory, University of Southern California</span></div>
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</div><p>The <em>Cannabis sativa</em> plant, also known as marijuana, contains compounds called cannabinoids, which can act on the brain to affect mood or consciousness. Tetrahydrocannabinol, or THC, is perhaps the best known of these compounds. Some evidence suggests that cannabinoids might help to treat certain health conditions. Possible uses include pain, inflammation, epilepsy, nerve cell diseases, and substance use disorders. However, some cannabinoids can cause side effects, such as dizziness, hallucinations, and paranoia. Some synthetic cannabinoids, such as K2 or Spice, can produce severe and even deadly reactions.</p>
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<p>Cannabinoids exert their primary effects in the brain by binding the human cannabinoid (CB<sub>1</sub>) receptor. Determining the detailed 3-D structure of this receptor at a fine level is important for potential drug development, as it reveals key details about how the receptor and drugs might interact. An international group of researchers set out to determine the structure of the CB<sub>1</sub> receptor. Their work was funded in part by NIH’s National Institute on Drug Abuse (NIDA). The study appeared on October 20, 2016, in <em>Cell.</em></p>
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||
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||
<p>The researchers synthesized a chemical called AM6538 that they designed to inactivate and help crystallize the CB<sub>1</sub> receptor. They slightly modified CB<sub>1</sub> as well to optimize it for crystallization. They then computed the 3-D structure of the CB<sub>1</sub>-AM6538 complex using X-ray crystallography, in which the angles and intensities of X-rays that bounce off a crystal structure are used to determine molecular shape.</p>
|
||
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||
<p>The crystal structure revealed that the CB<sub>1</sub> receptor has a complicated binding pocket with multiple subpockets. Based on prior findings, the scientists were able to predict how other cannabinoids would fit into the receptor. The model revealed insights into how long each cannabinoid might bind to the CB<sub>1</sub> receptor and how each might cause slightly different structural changes to the receptor. These findings provide clues to the mechanisms by which different cannabinoids can exert somewhat differing effects.</p>
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||
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||
<p>“Cannabinoids can produce very different outcomes, depending on how they bind to the CB<sub>1</sub> receptor,” says NIDA Director Dr. Nora D. Volkow. “Understanding how these chemicals bind to the CB<sub>1</sub> receptor will help guide the design of new medications and provide insight into the therapeutic promise of the body’s cannabinoid system.”</p>
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||
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<p>“This complex structure will allow chemists to design diverse compounds that specifically target portions of the receptor to produce desired effects,” says co-author Dr. Alexandros Makriyannis of Northeastern University.</p>
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</div><h2 class="label-above">Related Links</h2><ul class="spaced print-urls"><li><a href="https://www.nih.gov/news-events/nih-research-matters/high-resolution-imaging-technique-may-advance-drug-design" target="_top">High-Resolution Imaging Technique May Advance Drug Design</a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/designing-more-effective-opioids" target="_top">Designing More Effective Opioids</a></li><li><a href="https://www.drugabuse.gov/drugs-abuse/marijuana/nih-research-marijuana-cannabinoids" target="_top">NIH Research on Marijuana and Cannabinoids</a></li><li><a href="https://www.cancer.gov/about-cancer/treatment/cam/patient/cannabis-pdq" target="_top">Cannabis and Cannabinoids</a></li></ul><p class="footnote"><strong class="label-inline">References: </strong><a href="https://www.ncbi.nlm.nih.gov/pubmed/27768894">Crystal Structure of the Human Cannabinoid Receptor CB1.</a> Hua T, Vemuri K, Pu M, Qu L, Han GW, Wu Y, Zhao S, Shui W, Li S, Korde A, Laprairie RB, Stahl EL, Ho JH, Zvonok N, Zhou H, Kufareva I, Wu B, Zhao Q, Hanson MA, Bohn LM, Makriyannis A, Stevens RC, Liu ZJ. <em>Cell</em>. 2016 Oct 20;167(3):750-762.e14. doi: 10.1016/j.cell.2016.10.004. PMID: 27768894.</p><p class="footnote"><strong class="label-inline">Funding: </strong>NIH’s National Institute on Drug Abuse (NIDA), National Science Foundation, Ministry of Science and Technology of China, National Nature Science Foundation of China, Shanghai Municipal Government, ShanghaiTech University, and the GPCR Consortium.</p>
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<p><a href="https://www.nih.gov/news-events/nih-research-matters/research-context-can-we-slow-aging">Research in Context: Can we slow aging?</a></p>
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|
||
<p><a href="https://www.nih.gov/news-events/nih-research-matters/brain-changes-observed-during-pregnancy">Brain changes observed during pregnancy</a></p>
|
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|
||
<p><a href="https://www.nih.gov/news-events/nih-research-matters/research-context-detecting-cancer">Research in Context: Detecting cancer</a></p>
|
||
|
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<p><a href="https://www.nih.gov/news-events/nih-research-matters/risk-future-burden-dementia-united-states">Risk and future burden of dementia in the United States </a></p>
|
||
|
||
<p><a href="https://www.nih.gov/news-events/nih-research-matters/complete-wiring-map-adult-fruit-fly-brain">Complete wiring map of an adult fruit fly brain</a></p>
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<h3 class="block__title">About NIH Research Matters</h3>
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<p><strong>Editor:</strong> Harrison Wein, Ph.D.</p>
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<p><strong>Assistant Editors:</strong> Vicki Contie and Brian Doctrow, Ph.D.</p>
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<p><strong><em>NIH Research Matters </em></strong>is a weekly update of NIH research highlights reviewed by NIH’s experts. It's published by the <a href="/institutes-nih/nih-office-director/office-communications-public-liaison">Office of Communications and Public Liaison</a> in the <a href="/institutes-nih/nih-office-director">NIH Office of the Director</a>.</p>
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<p>ISSN 2375-9593</p>
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