Gender differences in subjective discontinuation symptoms associated with ketamine use

Abstract

BackgroundRecent substance abuse research indicates gender differences in the substance-related epidemiology, biological responses, progression to dependence, medical consequences and treatments. Studies exploring human sex-different responses to ketamine are rare and there has been no systemic survey of gender differences in ketamine use. Determining whether females are more susceptible than males to ketamine withdrawal symptoms and adverse effects is important, because it associated with treatment retention and outcome in drug users.MethodsThe Taiwanese juridical system has implemented a new regulation on ketamine in the year 2009. Ketamine users who are caught by the police, are mandated to attend an educational program. We recruited ketamine offenders from February 2010 to May 2012 at the Kunming branch of the Taipei City Hospital, where the educational classes are held. A designed questionnaire was performed to gather information about demographic characteristics, discontinuation symptoms, concomitant use of other substances, and subjective experience of memory impairment or urinary discomforts, and to compare the gender differences.ResultsA total of 1,614 ketamine users were surveyed and most of them were males (83.8%), with an average age of 26.3 ± 5.4 years. Female ketamine users presented significantly more discontinuation symptoms such as anxiety, dysphoria, and tremors compared with male users. 72.4% of total ketamine users smoked cigarettes concomitantly. Male ketamine users had a higher rate of concomitant betel nut use, while female ketamine users had a higher rate of concomitant hypnotic and alcohol use. 76% of total ketamine users reported cognitive impairment and 51.6% mentioned urinary symptoms. Furthermore, female ketamine users self-reported significantly greater levels of severity in cognitive impairment and urinary discomforts compared with male users. Less than 10% of total ketamine users in our study reported the desire to transfer for medical intervention or treatment, despite the high rates of discontinuation symptoms and negative physical side effects.ConclusionsGender differences were noted in the subjective experience of discontinuation symptoms, concomitant substance use, and severity of impairment related to ketamine use. However, the probable cause of the gender differences found in this study requires further investigation. We hoped our study will stimulate further research in this field.

Reinforcing properties of an intermittent, low dose of ketamine in rats: effects of sex and cycle

“…In humans, females are more sensitive to ketamine’s withdrawal symptoms (Chen et al 2014), and preclinical research from our lab and others has shown that female rodents respond to lower doses of ketamine than males in measures of antidepressant-like effects (Carrier and Kabbaj 2013; Franceschelli et al 2015; Zanos et al 2016). While ketamine’s abuse potential and reinforcing properties have not been addressed in female rats, a heightened responsiveness to cocaine (Lynch and Carroll 1999, 2000; Swalve et al 2016), opiates (Cicero et al 2003; Lynch and Carroll 1999), nicotine (Swalve et al 2016), cannabinoids (Fattore et al 2007), and phencyclidine (Carroll et al 2005; Carroll et al 2000) have been observed using different self-administration paradigms.…”

Depression in chronic ketamine users: Sex differences and neural bases

“…Women are more vulnerable than men to depression (Kessler, 2003). In a survey of over 1,600 chronic ketamine users females presented significantly more discontinuation symptoms such as anxiety, dysphoria, and tremors and reported more severe cognitive impairment compared with male users (Chen et al, 2014). Preclinical work also suggested sex differences in the behavioral effects of ketamine.…”

Mechanisms of Action and Persistent Neuroplasticity by Drugs of Abuse

“…However, recent studies have shown withdrawal effects from ketamine use. Female ketamine users may show more severe withdrawal-associated cognitive impairment than male users (Fattore et al, 2009;Chen et al, 2014). Furthermore, in humans the abuse potential of oral ketamine (65 and 100 mg) is robust enough to have it being suggested as a positive control for evaluating abuse potential of other psychedelic compounds (Shram et al, 2011).…”