Gabapentin reduced some physical THC withdrawal symptoms in mice

Gabapentin (10+ mg/kg) reduced paw tremors and head twitches during rimonabant-precipitated THC withdrawal. At 50 mg/kg, it restored withdrawal-suppressed progressive ratio responding (a measure of motivation). However, gabapentin did not affect locomotor activity, marble burying, tail suspension struggling, or plasma corticosterone levels during withdrawal.

Separate cohorts of male and female mice received THC (10 mg/kg) or vehicle for 5.5 days. On day 6, withdrawal was precipitated with the CB1 antagonist rimonabant (2-3 mg/kg). Gabapentin was tested across multiple behavioral measures including somatic signs, locomotor activity, conditioned place preference, progressive ratio responding, marble burying, tail suspension, and plasma corticosterone.

There are currently no FDA-approved medications for cannabis withdrawal. Gabapentin is already widely prescribed for other conditions and showed promise in a prior clinical trial for cannabis withdrawal, making this preclinical validation of its mechanism particularly relevant.

The selective efficacy of gabapentin on somatic and motivational symptoms but not stress-related measures suggests cannabis withdrawal involves multiple independent symptom domains that may require combination treatment approaches.

Precipitated withdrawal (using a CB1 antagonist) differs from natural withdrawal and may produce more intense acute symptoms. Some behavioral tests showed no gabapentin effect, limiting its utility as a standalone treatment. Sex differences were not the primary focus.