Chronic and Intermittent THC Histories Produced Different Withdrawal-Related Activity in Primates
In a primate experiment, abrupt cessation of chronic THC increased home-cage activity, while an antagonist challenge affected chronic and intermittent groups differently. Exposure history was part of the result, not merely background information.
Two regimens were compared
Ten rhesus monkeys were divided between chronic and intermittent THC regimens. Researchers recorded home-cage activity, temporarily discontinued chronic treatment and tested THC and the antagonist rimonabant. The chronic group had a long history of daily dosing.
Spontaneous and precipitated withdrawal were distinct
Stopping chronic THC increased activity within 24 hours, with effects observed over subsequent days. Rimonabant also increased activity dose-dependently in the chronic group but did not significantly increase activity in the intermittent group. The latter comparison should not be omitted when describing the antagonist finding.
The outcome was movement
More activity in this setting was interpreted as a dependence-related sign. It was not a direct measure of human distress, craving, insomnia or a complete clinical withdrawal syndrome. Lighting and normal daily activity patterns were relevant to the observations.
What this supports
The findings support physical dependence under the tested chronic regimen and show the value of continuous observation. Small groups, different administration schedules and selected laboratory histories limit translation. They cannot establish that every cannabis user will have the same symptoms or timetable. A human assessment still needs the actual exposure pattern, cessation history and documented functional or clinical changes.
Related analysis: the separate mouse withdrawal study.
Primary research
Wilkerson JL; Schulze DR; McMahon LR. Tolerance and dependence to Δ9-tetrahydrocannabinol in rhesus monkeys: Activity assessments. PloS one (2019). DOI: 10.1371/journal.pone.0209947.
