Ketamine for Depression: Why Social Isolation and Alcohol History Matter

Ketamine can treat depression, but its safety for repeated use in depressed patients with alcohol use disorder (AUD) is unclear, according to a new study (1^✔ ✔Trusted Source
Effects of Chronic Social Isolation Stress and Alcohol on the Reinforcing Properties of Ketamine in Male and Female Rats

Go to source). A history of isolation and alcohol use influences ketamine’s effects in a sex-dependent manner, highlighting the need for personalized depression treatment.

How Alcohol and Loneliness Affect Ketamine Use

To investigate this possibility, Mohamed Kabbaj and colleagues from Florida State University modeled aspects of human depression in rats using long-term isolation and assessed how loneliness and alcohol exposure alter ketamine intake.

The authors found that a history of isolation and alcohol use influence the rewarding properties of ketamine in a sex-dependent manner.

Female rats took ketamine more than males in general. Prior alcohol use increased female rat ketamine intake while subsequently changing synapse structure in a reward-related brain region.

In males, previous alcohol use and social isolation independently increased ketamine intake. Males that consumed alcohol during social isolation also experienced different synaptic changes in the reward-related brain region during ketamine intake than males who did not have alcohol during isolation.

This work suggests that clinicians should consider sex differences and alcohol use history when using ketamine to treat patients.

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According to the authors, this eNeuro study is informative for clinical research and treatment of major depressive disorder.

Reference:

1. Effects of Chronic Social Isolation Stress and Alcohol on the Reinforcing Properties of Ketamine in Male and Female Rats - (https://www.eneuro.org/content/early/2025/02/13/ENEURO.0452-24.2025)

Source-Eurekalert