Gabapentin reduced some physical THC withdrawal symptoms in mice | Research

The takeaway

Gabapentin reduced somatic withdrawal signs (paw tremors, head twitches) and restored motivation in mice undergoing precipitated THC withdrawal, but did not affect locomotion, stress hormones, or all behavioral measures.

Addiction medicine researchers, clinicians managing cannabis withdrawal, pharmacotherapy developers

Gabapentin reduced somatic THC withdrawal signs but not stress response

What the researchers found

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.

Why it matters

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 numbers in context

THC 10 mg/kg for 5.5 days; rimonabant 2-3 mg/kg precipitated withdrawal; gabapentin 10+ mg/kg reduced paw tremors and head twitches; 50 mg/kg restored progressive ratio responding; no effect on corticosterone, marble burying, or tail suspension

How the study worked

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.

What this study cannot tell us

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.

How to read the evidence

Well-designed preclinical study using multiple behavioral measures, but precipitated withdrawal model may not fully translate to human natural withdrawal.

When this study was published

Published in 2021.

The bigger picture

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.

Questions still open

Would gabapentin be effective in spontaneous (non-precipitated) cannabis withdrawal models? Can gabapentin be combined with other medications to address the stress and affective symptoms it did not improve?

Common questions

What is gabapentin?

Gabapentin is an FDA-approved medication for epilepsy and neuropathic pain that is increasingly used off-label for various psychiatric and substance use conditions. It modulates calcium channels and GABA signaling in the brain.

Could gabapentin help people quitting cannabis?

It showed selective benefit in mice, reducing physical symptoms and restoring motivation during THC withdrawal. A prior clinical trial also showed promise. However, it did not address all withdrawal symptoms, suggesting it might work best as part of a broader treatment approach.

Read the original research

Gabapentin attenuates somatic signs of precipitated THC withdrawal in mice.

Neuropharmacology, 190, 108554

View on PubMed ↗Publisher’s paper ↗

Citation

Eckard, M L; Kinsey, S G. (2021). Gabapentin attenuates somatic signs of precipitated THC withdrawal in mice.. Neuropharmacology, 190, 108554. https://doi.org/10.1016/j.neuropharm.2021.108554