A Review of the Nonmedical Use of Ketamine Use Users and Consequences

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• Published: 22 September 2014

Gender differences in subjective discontinuation symptoms associated with ketamine employ

Substance Abuse Handling, Prevention, and Policy volume 9, Article number:39 (2014) Cite this article

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Abstract

Background

Contempo substance abuse enquiry 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 than susceptible than males to ketamine withdrawal symptoms and adverse furnishings is important, because it associated with treatment retention and outcome in drug users.

Methods

The Taiwanese juridical system has implemented a new regulation on ketamine in the year 2009. Ketamine users who are caught past the police, are mandated to attend an educational program. We recruited ketamine offenders from Feb 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 assemble information almost demographic characteristics, discontinuation symptoms, concomitant use of other substances, and subjective experience of memory damage or urinary discomforts, and to compare the gender differences.

Results

A total of 1,614 ketamine users were surveyed and nigh of them were males (83.8%), with an boilerplate 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.iv% of full ketamine users smoked cigarettes concomitantly. Male ketamine users had a higher rate of concomitant betel nut use, while female ketamine users had a college charge per unit of concomitant hypnotic and booze use. 76% of full ketamine users reported cognitive impairment and 51.6% mentioned urinary symptoms. Furthermore, female person ketamine users self-reported significantly greater levels of severity in cerebral 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.

Conclusions

Gender 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 report requires further investigation. We hoped our study will stimulate further research in this field.

Background

Ketamine is an anesthetic derivative of phencyclidine (PCP) with dissociative, analgesic and psychedelic backdrop. Although ketamine is classified as a hallucinogen, it is widely used in a variety of anesthetic procedures in pediatric, obstetric and geriatric patients [1]. Moreover, the antidepressant effects of ketamine in treating refractory low were reported in recent years [two].

According to the latest systemic review by Morgan and Curran [three], there are now increasing concerns about the harmful physical and psychological consequences of repeated misuse of ketamine. Acute physical harms include adventure of decease from accidents, acute cardiac risk from poisoning; ketamine-induced chronic physical harms include ulcerative cystitis, renal dysfunction and 'thou-cramps'. Frequent, daily use is also associated with neurocognitive damage, and most robustly, deficits in working and episodic retentivity [4]. Psychological effects of chronic ketamine use were related to depression and psychosis [5]. Ketamine withdrawal symptoms characterized by anxiety, shaking, sweating, palpitations and carvings seem to exist primal problems in frequent ketamine users and have been published by many example studies [6–viii]. However, there has yet to be a coherent and agreed upon description of a specific ketamine withdrawal syndrome to guide handling and diagnosis. A rapid development of tolerance was demonstrated in ketamine users, and many frequent users are concerned near habit and report trying but failing to stop using ketamine. Ketamine dependence tin atomic number 82 to costly health services, which include the treatment of the habit and its related impairments in social functions, as well as the chronic physical health problems that will likely incur follow-up costs beyond the lifespan.

Recreational utilise of ketamine was start documented on the w coast of the United States in the early on 1970s [9]. Ketamine has not been a major drug of abuse within the past two decades, and only a few cases accept been reported during this fourth dimension [10, eleven]. Later on the ecstasy epidemic, ketamine use has get more popular in recent years effectually the globe, specially as a common club drug amidst the dance, rave, and squat political party scenes. It is also becoming popular in the Britain [12, 13], Commonwealth of australia [14], Hong Kong [15, 16], and Mainland Prc [17]. In the latest World Drug Report by United Nations Office on Drugs Control (UNODC) 2013 [18], Ketamine belong to new psychoactive substance (NPS) and non controlled past international drug conventions, only which may pose a public wellness threat. Part of ketamine'southward growing popularity in Due south-East Asia may be due to its lower condition in the regulatory systems and lower price point equally a substitute for the increasingly expensive 'ecstasy' or methamphetamine.

Ketamine has as well become a commonly driveling substance in Taiwan during recent years, especially among youths and adolescents [19–21]. Bear witness showed that almost ketamine users in Taiwan likewise used ecstasy (MDMA) concomitantly. Detected rates of MDMA and ketamine were found to be every bit high equally 76% and 47% respectively among rave political party participants in Taiwan [20]. Leung et al. [22] conducted a focus group with club drug users and noted that at that place was a special drug use sequence widely expert by Taiwanese poly-drug users. In a single drug utilise episode, MDMA was usually the commencement drug used, followed by ketamine and and so marijuana. This unique sequence of polydrug utilise in a single episode is called "Trinity".

Ketamine is scheduled as level III in the "Narcotic Harm Control Deed" in Taiwan. Pure ketamine use is regarded as an offense and non a crime. Ane reason for the increase in the abuse of ketamine in contempo years is the lack of restriction by authorities. Reports from the Ministry of Justice showed increase in both the amount of street ketamine seized by the police, besides as the number of offenders (namely drug dealers or traffickers). Around 3000 to 4000 offenders were caught by the police in Taiwan per month during the year 2012.

Contempo substance corruption research indicates gender differences in the substance-related epidemiology, social factors, biological responses, progression to dependence, medical consequences, co-occurring psychiatric disorders, and barriers to treatment entry, retentivity, and completion [23]. For examples, in alcohol drinking, women'south drinking-related bug appear to progress more quickly than those of men [24], and women report more severe problems and experience more health-related consequences from substance utilise [25]. Stimulants may enhance sex differences in the dopamine system in limbic regions, which may partly mediate sex departure in drug abuse [26]. Craving and relapse of drug seeking in abstinent individuals have too been institute to differ betwixt men and women, and there is robust show that women are more likely to initiate drug misuse and relapse into drug employ afterwards withdrawal than men [27]. In ecstasy utilize, gender was found to significantly moderate the relationship betwixt the consumption and design fluency [28]. When addicted to cocaine or amphetamine, women showed more than impairment in decision making than men [29]. Studies exploring human sex-different responses to ketamine are rare. An animal study by Winters et al, who compared the differing analgesic effects of ketamine in male and female rats, indicated that females were much more sensitive to ketamine than males [30, 31]. Moreover, female rats showed a greater sensitivity to ketamine neurotoxicity and brain neural loss compared to males [32]. Determining whether females are more susceptible than males to ketamine withdrawal symptoms and adverse furnishings is important, especially in cognitive deficits, considering it associated with treatment memory and upshot in drug users [33]. The aim of this study is to further the direction strategy for the current epidemic of ketamine abuse in Taiwan. The researchers nerveless information on relevant demographic and clinical data, then equally to clarify the pattern of ketamine use, the discontinuation symptoms, the progression of harm, users' willingness to seek handling, and gender differences among ketamine users in the Taipei metropolitan area.

Methods

Participants and procedures

In light of the increasingly astringent problem of ketamine abuse, the Taiwanese juridical organisation implemented a new regulation that focused on ketamine users beginning in 2009. This new regulation stipulates that offenders caught past the law for using ketamine (as evidenced by urine screen results) volition receive a fine ranging from 10,000 to 50,000 NT dollars and attend a mandatory educational class for 4-8 hours. The mandatory class presents an opportunity for the investigator to come into contact with ketamine users within a larger sample.

Nosotros recruited ketamine offenders from February 2010 to May 2012 at the Kunming co-operative of the Taipei City Hospital where the educational classes are held. Since nosotros were non aware of established questionnaires to examine ketamine-related problems, we designed a questionnaire to include demographic characteristics, historic period, reasons for initial use of ketamine, likes and dislikes during ketamine apply, experience of discontinuation symptoms related to ketamine, and current concomitant substance employ. The survey contained boosted questions regarding the degree of retention damage and urinary discomforts. Information most reasons for ketamine use and users' likes and dislikes during ketamine utilise was collected by open questions, while the rest of the data was gathered through checklist questions. Since the Chinese version of the pelvic pain and urgency/frequency (PUF) questionnaire has been shown to exist reliable and valid for assessment in patients with lower urinary tract symptoms associated with street-ketamine utilise [34], and the cutting-off value of the total score range from xiii-17 with detecting interstitial cystitis among different literature reviews [34, 35]. We divided items assessing for urinary discomforts into three groups: Nil, Mild, and Astringent, to separate the servility amid the ketamine users who may across the cut-off points. Aught indicates never experiences of the pelvic pain or urgency/frequency; Mild indicates symptoms such equally urgency/frequency occasionally just non usually; Severe indicates symptoms such equally both pelvic pain and urgency/frequency, or one of the symptoms accomplish usually or always, or having received clinical helps. The astringent group could indicate the total score higher up 11 in the PUF questionnaire. However, there was no known validated self-report scale to evaluate ketamine-related memory impairments. Therefore, we designed a self-report questionnaire that categorizes memory impairment into three levels of severity: Nil, Balmy, and Severe. Nil indicates no memory impairments; Mild indicates slight memory impairments; Severe indicates obvious signs of retentivity reject.

During the educational class, the research banana provided a comprehensive description of the questionnaire, and all subjects were informed that their legal status would non exist influenced by whether or not they participated in the study. The procedure was confidential. Participants were non required to identify themselves unless they wished to leave their personal information for referral to farther medical evaluation or intervention. The Institutional Review Board of Taipei Metropolis Hospital, which has been certificated by Forum for Ethical Review Committees in Asian and Western Pacific Region (FERCAP) has approved this study (TCHIRB-971212).

Data analysis

Demographic and clinical characteristics of the patients were analyzed past Educatee t-examination or Chi-square test. Statistical analyses were performed using SPSS version 12.0. Results were considered statistically significant at p < .05. age-adapted associations between genders and take chances of Logistic regression analysis was also conducted to appraise ketamine-related cerebral impairment or urinary symptoms.

Results

Demographics

Of the 1624 ketamine offenders, 10 either refused or failed to complete the questionnaire. Therefore, our analysis included data from 1614 participants (Mean age: 26.three ± v.4 years; Male to female ratio: 5:i). Demographic characteristics are displayed in Tabular array 1, with gender comparison. Most of them were males (83.iii%), single (88.0%) and employed (83.nine%). The average duration of ketamine apply was about 4 years.

Table 1 Demographics information and clinical data in ketamine users

Total size tabular array

Concomitant substance utilize and discontinuation symptoms

Among the ketamine offenders, 72.iv% smoked cigarettes and 16.five% consumed alcohol. It was found that more male than female users used betel nut concomitantly. Also, female person users used more hypnotics and alcohol than males. The prevalence of other concomitant substance employ among ketamine users is besides displayed in Table 1.

When stopping ketamine use, the virtually common discomfort mentioned by participants was fatigue (26.0%), followed by poor appetite (xx.4%) and drowsiness (19.1%). Cravings, as well as anxiety and dysphoria, were common psychological symptoms at the discontinuation of ketamine use, especially in females. In addition, iii-5% of participants experienced physical symptoms such equally palpitation, sweating or tremors during discontinuation. Gender differences in discontinuation symptoms are shown in Table ii. Female ketamine users presented with significantly more anxiety (23.four%), dysphoria (24.1%) and tremors (6.5%) compared with male users during ketamine discontinuation.

Table two Subjective reports of symptoms during ketamine discontinuation

Full size table

Cocky-report about the cognitive impairment, urinary discomfort, and motivation to seek medical intervention

22.four% of total ketamine offenders reported that their cerebral ability was severely dumb by ketamine use, particularly in females (27.5%). In improver, more half of the full participants had urinary symptoms. Compared with males, female person ketamine offenders were more likely to develop astringent cerebral impairment (OR, 95% CI =1.717, 1.075-2.741) and urinary symptoms (2.719, 1.501-4.928) according to their self-report. Gender differences in subjective reports of cognitive impairment and urinary tract symptoms amidst ketamine users are shown in Table iii.

Table 3 Subjective cognitive impairment and urinary tract symptoms among ketamine users and the adjusted odds ratios (AORs) between genders

Full size table

Despite 76% of ketamine users reporting cognitive harm and 51.6% mentioning urinary symptoms, only vii% of ketamine users in our report opted to seek medical intervention or treatment under our transfer, with also statistically significant gender difference (male: half dozen.1%, female:11.7%; p = .001).

Give-and-take

In this report, we explored the discontinuation symptoms of ketamine offenders in Taiwan, and examined the gender deviation. The results demonstrated that female ketamine users had more severe cocky-written report cognitive impairment and urinary symptoms related to ketamine utilize than male users. Our study is the first with a large sample size that showed a gender difference in the complications of ketamine apply. The possible implication of our findings volition be discussed.

Discontinuation symptoms

Pharmacologically, ketamine's main action is on glutamate, the major excitatory neurotransmitter in the brain. It is a non-competitive adversary at ane of the iii glutamate receptors: the Due north-methyl d-aspartate (NMDA) receptor [three]. Ketamine too has less prominent actions at other receptor sites. Information technology blocks muscarinic acetylcholine receptors and may potentiate the effects of gamma-aminobutyric acrid (GABA) synaptic inhibition. In addition, ketamine induces activation of dopamine release [36] and acts as a weak agonist at μ opioid receptors [37]. Ketamine's affinity to multiple receptors could theoretically explain its furnishings on noesis, mood, psychotic experiences and withdrawal symptoms. Even though nearly of the participants in this study are poly-drug users and the discontinuation symptoms reported here may have been the result of a combination of different substances, ketamine users related their symptoms to the discontinuation of ketamine in the questionnaire.

It is unclear if physical symptoms occur during ketamine withdrawal. Yet, the discontinuation symptoms mentioned in our questionnaire are quite like to alcohol withdrawal. In fact, booze consumption was found to reduce certain ketamine discontinuation symptoms, such as anxiety, shaking, sweating, palpitation, and low mood [6]. Ketamine discontinuation tin can result in glutamate rebound with symptoms reminiscent of NMDA over-activity in alcohol withdrawal [6]. Information technology is plausible that modified forms of alcohol withdrawal regimens can lessen symptoms of ketamine discontinuation.

Gender difference

Gender differences were found in the participants' subjective reports of discontinuation symptoms, every bit well as concomitant substance use and severity of impairment related to ketamine. In improver, female ketamine users reported a college proportion of booze or hypnotic consumption compared to males. This tendency may exist related to the significantly higher amounts of self-reported discontinuation symptoms such as anxiety and tremors in female person ketamine users. In an animate being study, it was suggested that the gonadal hormones in female rats played a critical part in enhancing the antidepressant-like effects of ketamine [38]. Therefore, we surmised that female person ketamine users tended to experience dysphoric mood more than frequently than males during ketamine discontinuation, as shown in our report.

A study about gender differences in abusers of amphetamine-type stimulants (ATS) and ketamine (G) in southwestern China [39] compared gender trends in ATS and ATS + G patients. For males, the ATS + K patients were more probable to develop psychotic disorders than ATS patients. For females, the ATS + One thousand patients were more than likely to develop cognitive impairment than ATS patients. Due to the primal part of the NMDA-receptor in learning and memory, both acute and chronic employ of ketamine exerts specific and wide-ranging effects on retentiveness systems [four]. In line with previous beast study, female ketamine users were more vulnerable to cognitive deficits compared with males. On the other hand, a UK report showed an absence of gender difference in urinary symptoms among recreational ketamine users [40]. Still, female ketamine offenders were more likely to develop severe urinary discomforts in our findings. This suggests that female ketamine users may experience a greater amount of impairment related to ketamine use, which may encourage them to seek medical intervention.

Biological mechanisms underlying female person-specific ketamine effects are largely unknown. Acute administration of ketamine has been reported to decrease serum sex hormones including estradiol, progesterone, and testosterone in female rats [41]. Information technology is possible that repeated ketamine may accept specific furnishings on women via sex hormones; however, the likely cause of the gender differences constitute in this study requires further investigation.

Limitation

Our results should exist interpreted with some limitations in mind. Offset, since participants were recruited while being mandated by the police force to nourish the class, it was hard to validate the actual frequency and amount of ketamine and concomitant substance employ, and thus the data related to substance use should exist underestimated. Nosotros designed the confidential self-report to accept favorable ascertainment. Second, in the absence of established questionnaires to examine ketamine-related problems (e.g., discontinuation symptoms), the questionnaires we used have not been studied to make up one's mind reliability and validity. There was no definition of cerebral impairment in the questionnaire, and then the severity may be inconsistent between individual. Third, the discontinuation symptoms reported in our study may have been the result of a combination of unlike substances; however, ketamine users related their symptoms to the discontinuation of ketamine in the questionnaire. Researchers should be cautious to generalize our results given the high comorbidity of substance employ disorder with other mental health issues. In this study, neuropsychiatric disorders or current affective state were not identified. Previous studies showed that the lifetime rates of mood and anxiety disorders are significantly higher amidst women than men, with and without substance-use disorders [42]. Associations between most substance apply disorders and independent mood and feet disorders were positive and pregnant [43]. It is of import to carry a more comprehensive psychiatric cess to make up one's mind whether substance apply may enhance vulnerability for these disorders, or lead to organic changes that manifest every bit a mood or anxiety disorder. Finally, there might be gender differences on how participants responded to the self-written report questionnaires. Gender was an of import demographic cistron associated with symptom reporting, and most physical symptoms are typically reported more than oft past women than by men [44]. We cannot exclude the potential furnishings of gender on self-reporting biases in this report.

Implications

Ketamine has had a turbulent history since its get-go use as a clinical anesthesia for humans in 1964 [45]. With its analgesic-anesthetic mechanisms and antidepressant result, ketamine is associated with a high potential for abuse or dependence. The pros and cons of ketamine utilize, as well as other areas of dubiousness regarding its use (e.g. antidepressant effect), deserve further studies in the time to come.

Despite several limitations generalizing data derived from our study, experience has shown us that investigating subjects with substance employ can exist extremely difficult. This is the showtime article demonstrating the correlation between gender and ketamine-related problems. Our study demonstrated that female ketamine users had more severe self-reported cognitive harm and urinary symptoms than male users. These findings were compatible with previous animal study. However, a lot of additional piece of work is required for a better understanding of gender differences in ketamine use. We hoped our study will stimulate further enquiry in this field. Currently, there are no guidelines for effective management of ketamine withdrawal effects or dependence [46]. As ketamine abuse and dependence grows, habit services need to be amend informed of the furnishings of this drug, especially amongst young females. Policies emphasizing the increased vulnerability to ketamine-related adverse effects in female person users compared with male users and offer the opportunity to enhance medical accessibility may improve efforts to forbid progression of ketamine dependence. Further studies should aim to address the wellness problems experienced by this group and explore the best approach to treat ketamine addiction.

Conclusions

Discontinuation symptoms and concrete side-effects are not uncommon in these ketamine offenders. Gender differences were noted in the subjective feel of discontinuation symptoms, concomitant substance use, and severity of impairment related to ketamine employ. Additional piece of work is required for a amend understanding of the gender differences establish in this study. Ketamine users in Taiwan are generally relatively young; therefore, further studies should be conducted to increase the availability and accessibility of effective treatment interventions, and preventative public education.

Abbreviations

PCP:

Phencyclidine

UNODC:

United Nations Role on Drugs Control

NPS:

New psychoactive substance

MDMA:

iii,4-methylenedioxy-Northward-methylamphetamine

NMDA:

Due north-methyl d-aspartate

GABA:

Gamma-aminobutyric acid.

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Acknowledgements

This study was supported past Taipei City Government (99001-62-050) and granted from National Science Quango, Taiwan (NSC 101-2314-B-532 -002 -MY2). The authors wish to limited their deepest gratitude to all participants of this report.

Author information

Affiliations

1. Department of Addiction Scientific discipline, Taipei City Hospital and Psychiatric Heart, 309 Songde Route, Xinyi Commune, Taipei, 110, Taiwan

   Wen-Yin Chen, Ming-Chyi Huang & Shih-Ku Lin

2. Department of Psychiatry, College of Medicine, Taipei Medical University, Taipei, Taiwan

   Ming-Chyi Huang & Shih-Ku Lin

Corresponding author

Correspondence to Shih-Ku Lin.

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Competing interests

The authors declare that there is no conflict of interest of this study.

Authors' contributions

YWC and SKL designed the protocol and carried the survey. They gathered and analyzed the written report's data, and wrote the first draft of the manuscript. MCH assisted with the report's pattern and in the preparation of this manuscript. All authors read and approved the concluding manuscript.

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Chen, WY., Huang, MC. & Lin, SK. Gender differences in subjective discontinuation symptoms associated with ketamine use. Subst Abuse Treat Prev Policy 9, 39 (2014). https://doi.org/x.1186/1747-597X-9-39

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• Received: 27 December 2013

• Accepted: 08 July 2014

• Published: 22 September 2014

• DOI : https://doi.org/10.1186/1747-597X-ix-39

Keywords

• Ketamine
• Epidemiology
• Discontinuance symptoms
• Gender difference

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Source: https://substanceabusepolicy.biomedcentral.com/articles/10.1186/1747-597X-9-39

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