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On her 18th birthday, on March 11, 1976, Jones gained control of her saved earnings from her work in Family Affair, about $180,000 ($0.81 million today) as well as an undetermined amount, though in excess of $100,000 ($0.45 million today), of U.S. Savings Bonds, both of which had been held for her in a trust fund. Jones and her brother Paul then rented an apartment together, not far from their mother.

Shortly before noon on August 28, 1976, after partying in the beach town of Oceanside, California, with her new boyfriend Allan "Butch" Koven and others, Jones was found dead in a bedroom of a house belonging to the father of a 14-year-old friend named Helen Hennessy. The coroner's report listed her death as a drug overdose, later ruled accidental; cocaine, PCP, Quaalude, and Seconal were found in her body during an autopsy toxicology examination. The police report also indicated a small vial of blue liquid next to Jones at the scene, which was never identified. The coroner who examined Jones reported she died from one of the most severe drug overdoses he had ever seen. Jones was 18 years old.

Six days after Jones' death, Dr. Don Carlos Moshos was arrested and charged with illegally prescribing Seconal to Jones, among other drugs-for-profit charges from a concurrent undercover criminal investigation. An envelope with Moshos' business address was present at Jones' scene of death, specifying a drug found in Anissa's toxicology report (Seconal), its dosage (1.5 gr), quantity (50), and the recipient's last name (Jones). Moshos was charged with 11 offenses, including second-degree murder; while awaiting trial, Moshos died on December 27, 1976, four months after Jones. Although the murder charges were dropped before his death, Moshos' estate was sued by Jones' surviving family for $400,000; in July 1979, the verdict found him 30% liable and Jones 70% responsible for her death, and the resulting judgment was reduced to $79,500 ($357,200 today).

In 1975, Jones was invited to audition for the role of Iris "Easy" Steensma in Taxi Driver but turned it down. Jodie Foster would go on to win the role and, resultingly, cinematic fame.

However, Jones soon began shoplifting and taking drugs. In 1975, she dropped out of high school altogether and briefly worked at a Winchell's Donuts shop in Playa Del Rey. She reportedly felt embarrassed whenever customers recognized who she was.

Anissa's father, John Paul Jones, died of heart disease, March 7, 1974, age 44. On March 15, 1984, Jones' brother Paul died of a drug overdose. He was 24 years old. Jones' mother Mary Paula Jones died in Detroit, Michigan of natural causes on January 14, 2012.

Meanwhile, Brian Keith kept in touch with Jones through letters and offered her a young-adult role on The Brian Keith Show (1972–1974). Keith told her she would not need to audition for the part, but by then, Jones no longer wanted to work in television.

Jones' Buffy character had a doll named Mrs. Beasley, which she claimed talked to her, often making funny comments. When the show became a hit, the doll was marketed by Mattel (with Georgia Schmidt providing the doll's voice) and became a best-seller in North America. Mattel also marketed two other dolls, patterned after Buffy: one in the size of its "Tutti" line of dolls and another in its talking "Small Talk" line, which featured eight different phrases (using Jones' voice). Jones took part in several other lucrative Family Affair product marketing campaigns such as Buffy paper dolls, lunch boxes, two clothing lines, coloring books, and a 1971 cookbook with her picture on the cover.

Family Affair was cancelled abruptly by CBS' "rural purge" campaign in 1971, after five seasons and 138 episodes. By then, Jones was 13 years old and said she was happy at the thought of no longer needing to be seen with the Mrs. Beasley doll. She wanted to act in films, but Jones could not find the kind of work she wanted: she auditioned for the part of Regan MacNeil in the film The Exorcist (released in 1973), but the director, William Friedkin, felt that with Family Affair still in popular consciousness at the time through syndicated daytime reruns, movie audiences might have thought "Buffy" was the one being possessed. Linda Blair was cast instead.

Family Affair was a grueling, full-time, year-'round job for Jones: she was often either shooting the show or promoting it in public, seven days a week. Through each of the first three seasons, up to 30 programs were filmed for broadcast. This contrasts with later American episodic television that produce runs of 24 shows per season or less, allowing more breaks in filming and requiring fewer promotional appearances for the principal actors. In April 1969, Jones broke her right leg in a playground accident (she rebroke her leg later that August in an accident on the beach near her home), and the producers had her injury written into the show's scripts.

Jones appeared on Rowan & Martin's Laugh-In (three cameos) on March 11, 1968, was featured twice on The Mike Douglas Show (March 6, 1969 and December 22, 1969), and then featured on The Dick Cavett Show on February 25, 1971, along with actor/singer Sammy Davis Jr. and pianist Garrick Ohlsson. The Cavett appearance was her final appearance on television.

Jones was eight when her acting skills drew the attention of television producers, and she was cast as Ava Elizabeth "Buffy" Patterson-Davis on the CBS sitcom Family Affair (1966). In the opening plotline, Buffy, her twin brother Jody (Johnny Whitaker), and older sister Cissy (Kathy Garver) are sent to live with their Uncle Bill (Brian Keith) and his valet Mr. French (Sebastian Cabot) a year after the children's parents die in a car accident (the DVD collection notes mistakenly state "plane accident"). By July 1969, the series had become a hit, and Jones became a popular child celebrity. She also played the role of Carol Bix in the Elvis Presley comedy film The Trouble with Girls (1969).

Jones' parents had initiated a bitter divorce in 1965 and carried on a long feud over custody of Anissa and her younger brother, Paul. In 1973, custody of both children was awarded to their father, but he died of heart disease shortly thereafter.

When Jones was two years old, her mother enrolled her in dance classes. In 1964, when Jones was six, Mary Paula took her daughter to an open audition for a breakfast cereal commercial, which became Jones' first television appearance.

Mary Anissa Jones (/ə ˈ n iː s ə / ; March 11, 1958 – August 28, 1976) was an American child actress known for her role as Buffy on the CBS sitcom Family Affair, which ran from 1966 to 1971. She died from combined drug intoxication at the age of 18.