The Russian, who started the year by winning the Australian Open, has lost form in recent months, losing to Juan Carlos Ferrero in Monte Carlo last week and suffering a surprise 6-4, 6-4 defeat in his first match in Barcelona.
"I've had a poor two months after Australia and it's very frustrating to be in this position," said the 25-year-old.
"I've gradually lost all my confidence and that is why I lost today. My opponents know that I'm struggling and they obviously take advantage.
"I'm feeling a combination of frustration and pressure. I want to come back as fast as possible especially with the tournaments in Rome and Hamburg coming up, but there's no strategy to solve the problem it's just a question of running hard, fighting and waiting for my opportunity."
Acasuso, who beat Safin in their only previous meeting in the World Team Cup in Germany in 2002, edged the first set and made the crucial breakthrough in the fifth game of the second when he came to the net to earn a third break point.
Safin, a winner in Barcelona in 2000 and finalist in 2003, lost the game to trail 3-2 and began to lose his temper as he struggled to cope with Acasuso's heavy ground strokes and the partisan crowd got on his back.
The Argentine set up three match points when he caught Safin out with a delicate drop shot and won the match after the Russian netted a backhand return.
"He surprised me a little," Safin said. "He was lucky on a lot of points, but was very solid, he served quite well and made no serious errors."
The Russian was also forthright in his comments about the reception he received from the Barcelona crowd.
"I wasn't angry with the crowd, they were angry with me. But if they don't like what I do then I won't come, the tournament can save some money and I can save some time and everyone will be happy."
Despite his evident frustration, however, Safin remained philosophical about recovering his form before next month's French Open.
"It's only a sport, so I don't want to get carried away about it," he said. "But it's clear that no one likes to be in this position. I'm experiencing a low at the moment, but it can only get better -- when is the question though.
"If I continue fighting my opportunity will come and I'm sure that will be before French Open. Maybe I just need that little bit of luck to give me that extra push."