Phoebe’s surrogacy. Ross and Emily’s short-lived marriage. Monica and Chandler in Vegas. Matthew Perry might not remember any of it, according to comments he made during an interview with BBC radio host Chris Evans.

When asked which episode of Friends was his least favorite, the actor replied, “I think the answer is, I don’t remember three years of it, so none of those. I was a little out of it at the time. Somewhere between seasons three and six.”

Perry, now an outspoken addiction recovery advocate, famously struggled with addictions to alcohol and several prescription drugs while filming the beloved sitcom. In 1997, the actor completed a 28-day program for Vicodin addiction, later telling Larry King that he took the painkiller “mostly just to not drink as much as I was.” In 2001, near the end of Perry’s purported memory gap, he entered a rehab hospital to recover from his use of Vicodin, methadone, amphetamines, and alcohol.

But can alcohol and prescription drugs really wipe away three years worth of filming or, at least, make them almost impossible to remember? While the particulars of Perry’s condition aren’t public, substance abuse can indeed have powerful effects on human memory, ranging from mild impairment to complete loss.

Alcohol and memory loss are, of course, old friends. In his BBC interview, Perry said that he was never drunk while filming Friends but that he was often “painfully hungover.” But even apart from the well-known effects of blackouts on a night out, alcohol can impair long-term memory in other, more permanent ways.

As brain researcher Dr. Aaron White wrote for the National Institute on Alcohol Abuse and Alcoholism (NIAAA), “Alcohol primarily interferes with the ability to form new long-term memories, leaving intact previously established long-term memories and the ability to keep new information active in memory for brief periods.”

In other words, it would be entirely possible to film a TV show but have difficulty recalling the experience years later. A large body of animal studies, as Dr. White observes, have shown that alcohol consumption can disrupt or damage the hippocampus, a region of the brain that aids in forming new long-term memories. “As the amount of alcohol consumed increases,” he wrote, “so does the magnitude of the memory impairments.”

The amount of alcohol that Perry consumed was indeed substantial. In 2002, Perry told People that, for a time, he was drinking “probably a quart of vodka a day.”

There are other, more serious long-term memory problems associated with increased alcohol consumption as well. Because many alcoholics suffer from a thiamine deficiency, they are at an increased risk for developing a rare disorder called Korsakoff’s syndrome, which, as the NIAAA puts it, makes it difficult to “lay down” new information. Clinically, this symptom is known as anterograde amnesia, famously depicted in the 2000 film Memento.

“For example,” the Alzheimer’s Association notes, “individuals [with Korsakoff’s syndrome] may seem able to carry on a coherent conversation, but moments later be unable to recall that the conversation took place or to whom they spoke.”

Perry didn’t develop Korsakoff’s syndrome—those who suffer from it typically require long-term residential care—but the disorder demonstrates the full range of alcohol’s ability to damage long-term memory.

But what about Perry’s other, related battles with Vicodin, methadone, and amphetamines? In his 2002 People profile, Perry said that he was taking “an insane number of [Vicodin] pills” at the height of his addiction to the opioid painkiller.

Much of the research on these drugs focuses on their varying effects on “working memory” rather than long-term memory. As defined by British psychologist Alan Baddeley, working memory “refers to a brain system that provides temporary storage and manipulation of the information necessary for such complex cognitive tasks as language comprehension, learning, and reasoning.” Adding two numbers in your head, for example, relies heavily on working memory, and, in that sense, it is comparable to a computer’s RAM rather than, say, the hard drive where information is stored long-term.

While it’s a safe bet, then, that Perry’s problems with prescriptions contributed to his behavior on set—he told People that he was “sleepy and shaky at work”—his self-reported three-year memory gap probably had more to do with that daily quart of vodka than it did with pills.

And while Perry may not remember a large fraction of Friends, he has gone on to help others recover from their own struggles with addiction and substance abuse. In addition to his frequent public speaking and writing on the issue, the actor turned his Malibu property into an addiction recovery center and received a 2013 Champion of Recovery award from the White House. “It wasn’t a question of strength,” Perry recently told the BBC of his recovery. “It was a question of whether I wanted to live or die—that was the real decision. I’m happy to say that I chose life.”