Gavin Christopher Newsom was born in San Francisco, California, to Tessa Thomas (nee Menzies) and William Alfred Newsom III, a retired state appeals court justice and attorney for Getty Oil. He is a fourth-generation San Franciscan. His father is of mostly Irish descent; one of Newsom's maternal great-grandfathers, Scotsman Thomas Addis, was a pioneer scientist in the field of nephrology and a professor of medicine at Stanford University. Newsom is the second cousin, twice removed, of musician Joanna Newsom.

In 2014, Newsom was the only statewide politician to endorse California Proposition 47, a piece of legislation that decriminalized nonviolent offenses like drug and property crimes, turning them into misdemeanors as opposed to felonies. In July 2015, Newsom released the final report of the Blue Ribbon Commission on Marijuana Policy, which he had convened with the American Civil Liberties Union of California in 2013. The report's recommendations to regulate marijuana were intended to inform a legalization measure on the November 2016 ballot. Newsom supported the resulting measure, Proposition 64, which legalized cannabis use and cultivation for California state residents who are 21 or older. In response to pro-enforcement statements made by Press Secretary Sean Spicer, Newsom sent a letter on February 24, 2017, to Attorney General Sessions and President Trump, urging them not to increase federal enforcement against recreational cannabis firms opening up in California. He wrote, "The government must not strip the legal and publicly supported industry of its business and hand it back to drug cartels and criminals ... Dealers don't card kids. I urge you and your administration to work in partnership with California and the other eight states that have legalized recreational marijuana for adult use in a way that will let us enforce our state laws that protect the public and our children, while targeting the bad actors." Newsom responded to comments by Spicer which compared cannabis to opioids saying, "Unlike marijuana, opioids represent an addictive and harmful substance, and I would welcome your administration's focused efforts on tackling this particular public health crisis."

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