大規模基因研究發現與大麻成癮有關的基因

來自超過一百萬個基因組的數據為過度使用大麻及其與其他疾病的關係提供了新的見解。

Lilly Tozer / 2023 年 11 月 20 日 / 新聞 / Nature

吸食大麻在某些國家是合法的，但長期吸食和成癮會對健康產生負面影響。

圖片來源：Raul Arboleda/AFP via Getty

透過分析超過一百萬人的基因組，研究人員發現了可能與大麻成癮有關的基因。 他們還發現，基因組中的一些相同區域與其他健康狀況有關，例如肺癌和精神分裂症。

康乃狄克州紐黑文市耶魯大學醫學神經科學家、這項今日發表於《自然遺傳學》研究的合著者丹尼爾·利維(Daniel Levey) 表示，這些發現證明大麻成癮「如果使用量增加，可能會帶來巨大的公共健康風險」。

娛樂性吸食大麻在 8 個國家是合法的，48 個國家已將該藥物用於治療慢性疼痛、癌症和癲癇等疾病上合法化。 但三分之一的吸食大麻的人最終會上癮，或以損害健康的方式使用該藥物。 先前的研究顯示，存在遺傳因素，並顯示出有問題的大麻使用與某些癌症和精神疾病之間的關聯。

權衡大麻的危險

利維說，吸毒和成癮會受到人們基因和環境的影響，這使得研究它們變得極其困難。 但該團隊能夠在先前的工作基礎上，納入來自其他來源的遺傳訊息，主要是百萬退伍軍人計畫——一個位於美國的大型遺傳資料庫，旨在改善退伍軍人的醫療保健。 該分析涵蓋了多個種族群體，這是首次的針對大麻濫用的基因研究。

除了確定可能涉及的基因外，研究人員還發現過度使用大麻和精神分裂症之間存在雙向聯繫，這意味著這兩種情況可以相互影響。 倫敦國王學院的精神病學家兼科學家瑪爾塔·迪·福蒂 (Marta Di Forti) 表示，這項發現很有趣。 她說，吸食大麻是精神分裂症「最可預防的風險因素」，並補充說，這項研究中檢查的遺傳數據類型將來可用於識別和支持那些因吸食大麻而罹患精神疾病的風險增加的人。

該研究的合著者、耶魯大學精神病遺傳學家喬爾·格倫特(Joel Gelernter) 表示，有關大麻使用與健康狀況之間的生物機制的更多信息將為政策和醫療實踐提供更好的證據基礎。

他補充說，研究人員需要繼續鞏固這些知識，並利用這些數據來了解醫療和娛樂大麻使用的健康風險。 迪·福蒂對此表示同意，並補充說，調查該藥物的給藥方式以及使用者消耗了多少影響精神成分的四氫大麻酚（THC）之具體情況也很重要。

doi：https://doi.org/10.1038/d41586-023-03629-8

參考文獻：

1. Levey, D. F. 等。 《自然基因》。 https://doi.org/10.1038/s41588-023-01563-z（2023）。

2. Johnson, E. C. 等。 《剌胳針精神病學》 7, 1032–1045 (2020)。

Massive genetic study finds genes linked to cannabis addiction

Data from more than one million genomes offer fresh insights into excessive cannabis use and its relationship to other diseases.

Lilly Tozer / 20 November 2023 / NEWS / Nature

Taking cannabis is legal in several countries, but long-term use and addiction can have negative health consequences.Credit: Raul Arboleda/AFP via Getty

By analysing more than one million people’s genomes, researchers have identified genes that could be linked to cannabis addiction. They also found that some of the same regions in the genome are associated with other health conditions, such as lung cancer and schizophrenia.

The findings are evidence that cannabis addiction “could have substantial public-health risks if the usage increases”, says Daniel Levey, a medical neuroscientist at Yale University in New Haven, Connecticut, and a co-author of the study, published today in Nature Genetics.

Taking cannabis recreationally is legal in 8 countries, and 48 countries have legalized medicinal use of the drug for conditions including chronic pain, cancer and epilepsy. But one-third of people who take cannabis end up becoming addicted, or using the drug in way that is damaging to their health. Previous studies have suggested that there is a genetic component, and have shown links between problematic cannabis use and some cancers and psychiatric disorders.

Weighing the dangers of cannabis

Drug taking and addiction can be influenced both by people’s genes and by their environment, which makes them extremely difficult to study, says Levey. But the team was able to build on previous work2 by including genetic information from additional sources, predominantly the Million Veterans Program — a large US-based genetic database that aims to improve health care for former military service members. The analysis encompassed multiple ethnic groups, a first for a genetic study looking at cannabis misuse.

As well as identifying genes that might be involved, the researchers saw a bi-directional link between excessive cannabis use and schizophrenia, meaning that the two conditions can influence each other. This finding is intriguing, says Marta Di Forti, a psychiatrist-scientist at King’s College London. Cannabis use “is the most preventable risk factor” for schizophrenia, she says, adding that the type of genetic data examined in the study could be used in future to identify and support people at increased risk of developing psychiatric disorders through cannabis use.

More information about the biological mechanisms that connect cannabis use with health conditions will provide a better evidence base for policy and medical practice, says study co-author Joel Gelernter, a psychiatric geneticist at Yale University.

He adds that researchers need to continue to build on this knowledge and use the data to understand the health risks of both medical and recreational cannabis use. Di Forti agrees, adding that it will also be important to investigate the specifics of how the drug is administered, and how much of the psychoactive component tetrahydrocannabinol (THC) users consume.

doi: https://doi.org/10.1038/d41586-023-03629-8

References

1. Levey, D. F. et al. Nature Genet. https://doi.org/10.1038/s41588-023-01563-z (2023).
2. Johnson, E. C. et al. Lancet Psychiatry 7, 1032–1045 (2020).