THC withdrawal in mice disrupted both motivation and attention, but only motivational deficits persisted during abstinence

After 5 days of twice-daily THC (10 mg/kg), rimonabant-precipitated withdrawal caused longer session times, longer response latencies, more errors, and slower error correction in THC-treated mice. During the 3-day abstinence window, motivational measures (response latency, session duration) remained disrupted in THC-treated mice, but attentional measures (errors, latency to switch after error) returned to baseline.

Male and female C57BL/6J mice trained on a response alternation task with spatially distinct response options. After 5 days of THC or vehicle, withdrawal precipitated with rimonabant (CB1 inverse agonist) on day 6, then 3 days of monitored abstinence.

This study distinguishes between precipitated and spontaneous cannabinoid withdrawal for the first time in the same subjects, revealing they may be qualitatively different states rather than just different intensities of the same withdrawal syndrome.

If motivation and attention are differentially affected during different phases of cannabis withdrawal, treatment strategies may need to evolve as patients move from acute to post-acute withdrawal, addressing motivational deficits that outlast cognitive ones.

Mouse model with high THC doses. Precipitated withdrawal using rimonabant is more abrupt than natural human cessation. Short 5-day exposure and 3-day abstinence window. Response alternation task may not fully capture the complexity of human motivation and attention.