Spiderhead is a state-of-the-art penitentiary experimenting with the effects of research chemicals. The test subjects, technically prisoners of the state, are volunteers for the project aiming to reduce their sentence time. The program is overseen by the sympathetic and hospitable Steve Abnesti, along with his assistant Mark. The prisoners have their own rooms, do chores, and are free to roam without guard supervision. The subjects go through daily test runs of various drugs, all of which alter their emotions and their perceptions of their surroundings.
Inmate Jeff, still reeling from having killed his friend whilst drunk driving, is given N-40, a “love drug”, which distorts his senses and drives him to have sex with two of his fellow inmates. Steve asks him to choose which one of them to give Darkenfloxx, a drug that induces intense fear and psychological pain. He declines to choose, claiming he feels nothing in particular for either one of them after the effects of the love drug had worn off.
The next day, Steve tells him that the “higher ups” have chosen that he and the younger of the two women, Heather, must be injected with a dose, though it will only last five minutes. Jeff reluctantly agrees, and to his horror, Heather commits suicide while on the Darkenfloxx after she damages her MobiPak, the device that administers the drugs. This causes Mark to doubt their work in the facility. As Steve rushes out of the projection room, he drops his keys. Jeff unlocks Steve’s desk compartment, discovering that there are no “higher-ups”: the prison is run by Abnesti Pharmaceuticals. The drugs were named from a bingo card.
Steve and Jeff get high together on a laughing drug, as Steve also has a MobiPak installed. Steve tells Jeff that his father abandoned him as a child. Jeff confesses to Lizzy, an inmate he is close with, that he not only killed his friend in the car accident but his girlfriend as well. Lizzy hugs him and they kiss. Steve notices Jeff’s feelings for Lizzy. Mark becomes doubtful of Steve’s motives, and he breaks down when Jeff confronts him.
When Steve asks Jeff to administer Darkenfloxx to Lizzy, Jeff takes control of Steve’s MobiPak and forces him to admit the true goal of the program is to test a compliance drug, B-6. The other drugs are merely side projects being used to put B-6 to the ultimate test: whether or not they would harm their love when commanded to. The entire time inmates had been consenting to the various tests, they had really been under the influence of the obedience drug. In addition, Steve informs Jeff that he had in fact finished his sentence seven months previously, while Lizzy’s appeal for release had passed the previous week. Jeff forces Steve to open the door of the main entrance to free Lizzy and then tries to order him to hand over the pocket knife. Steve resists and instead takes his phone and enables all four vials of Darkenfloxx in Lizzy’s MobiPak, causing her to behave hysterically and attempt suicide. The two fight for control and Jeff is able to disarm Steve, damaging his MobiPak in the process. Jeff rushes to save Lizzy, successfully removes the vials of Darkenfloxx and tells her he loves her, but Steve gets up and orders the other inmates to apprehend Jeff and Lizzy. They are able to escape from Spiderhead after overpowering some of the other inmates and locking the main door behind them. Mark and the police are now approaching the island as Steve escapes on his floatplane, but he joyously crashes into a mountain as he is now high off of his damaged MobiPak. Meanwhile, Jeff and Lizzy take the remaining motorboat and escape.
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