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Link between personality and response to THC exposure

Tetiana Kardash, Dmitry Rodin, Michael Kirby, N S Davis, Igor Koman, Jonathan Gorelick, Izhak Michaelevski, Albert Pinhasov

bioRxiv (Cold Spring Harbor Laboratory) June 17, 2019 preprint DOI: 10.1101/674044 via OpenAlex

Summary

AI-generated from the abstract

Mice bred for stress resilience (socially dominant) or stress sensitivity (socially submissive) responded differently to delta-9-tetrahydrocannabinol (THC). At a high dose (15 mg/kg), submissive mice developed a place aversion, while dominant mice showed no preference or aversion. After a six-week washout, the low dose (1.5 mg/kg) reduced depressive-like behavior in submissive mice, but the high dose increased it in dominant mice. High-dose THC raised serum corticosterone in both groups. The findings suggest that individual differences in stress vulnerability and dominance influence cannabis responses and should be considered when prescribing THC-containing medications.

Study at a glance

Characteristics Experimental study
Population Selectively-bred stress-resilient socially dominant and stress-sensitive socially submissive mice
Intervention delta-9-tetrahydrocannabinol (THC)
Dose 1.5 mg/kg and 15 mg/kg
Duration Short-term repeated treatment, with a 6-week washout period
Topics Anxiety
Keywords Anxiolytic Population Euphoriant Paranoia
Key finding THC dose and mouse stress phenotype interact to produce opposing effects on place preference and depressive-like behavior.

Abstract

ABSTRACT The effects of cannabis reported by users range from experiences of euphoria and anxiolytic effects to paranoia, anxiety, and increased risk of depression. Attempts to reconcile the apparent contradictions in user response have not been conclusive. Here, we utilized selectively-bred stress-resilient socially dominant (Dom) and stress-sensitive socially submissive (Sub) mice to elucidate this contradiction. Following short-term, repeated treatment with delta-9-tetrahydrocannabinol (THC) at two different doses (1.5 mg/kg and 15 mg/kg), Sub mice presented significant place-aversion in a Conditioned Place Preference paradigm at a high dose, whereas Dom mice displayed no place preference or aversion. Forced Swim test conducted after 6-week of washout period, revealed differential impact of the two THC doses depending upon behavioral pattern. Specifically, the low dose alleviated depressive-like behavior in Sub mice, while the high dose produced the opposite effect in Dom mice. Interestingly, corticosterone concentration in serum was elevated at the high dose regardless of the mice-population tested. We conclude here that differences in dominance behavior and stress vulnerability are involved in the regulation of cannabis response among users and should be considered when prescribing THC-containing medications to patients.

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