Ketamine Users Research Articles

Patterns of use, harm reduction strategies, and their relation to risk behavior and harm in recreational ketamine users

ABSTRACTBackground: Recent studies have shown that ketamine use has serious adverse consequences. However, no studies have focused on the strategies that users carry out to protect themselves from such potential harm. Objectives: (i) analyze harm reduction strategies, risk behaviors, and harms in nonmedical/recreational ketamine users; (ii) analyze the association of their harm reduction strategies and risk behaviors with harms they report. Methods: An anonymous cross-sectional web-based survey of 462 persons who had used ketamine in the past year. We designed a questionnaire to collect information on their risk behaviors, harm, and harm reduction strategies. Results: The harms most reported were unexpected confusion (58.2%), memory impairment (57.4%), and abrupt mood/behavior changes (49.6%). The most frequent strategies were spacing out sessions (60.8% always/almost always did this), spacing out doses within a session (54.5%), and limiting the amount and not going over it (41.3%). The use of these three strategies was related to a lower probability of perceiving negative consequences associated with ketamine use, including memory impairment, healthcare assistance, psychological dependence, and risk behaviors related to driving under the influence of ketamine. Conclusions: This study provides empirical evidence on strategies related to the lower probability of harm associated with ketamine use as employed by recreational ketamine users. Our findings suggest that efforts to minimize harm from ketamine use should focus on increasing awareness of potential harms and the use of identified harm reduction strategies.

Reliability, convergent and structural validity and cut-off score of the Severity of Dependence Scale for recreational ketamine users

Background and aimsThere is a lack of instruments for measuring ketamine substance use disorders. The aims were (i) to estimate the reliability and provide evidence of validity of the Severity of Dependence Scale (SDS) in a sample of recreational users, and (ii) propose a cut-off point to determine the presence of dependence. MethodsWe conducted a web-based cross-sectional survey with recreational users who accessed webs related to recreational drug use and harm reduction. 264 recreational ketamine users who had taken it in the past month participated in the study. The Spanish version of the SDS was used. Information on ketamine use-related problems and ketamine use patterns was also collected. ResultsThe reliability estimation calculated by the Cronbach’s alpha coefficient was 0.776. SDS showed evidence of convergent validity based on relationships with other variables. Two comparisons were made in this study to analyze the Receiver Operating Characteristic Curve. For frequency of use in the last month the area under curve (AUC) was 0.835 (CI=0.775-0.895) with optimal discrimination at an SDS score of 3. For having been in treatment for decreasing or quitting ketamine use the AUC was 0.902 (CI=0.840-0.963) and the cut-off point was 4. Confirmatory factor analysis showed a one-dimensional structure when Items 3 and 4 were correlated. ConclusionsThis study has provided evidence of reliability and validity of the ketamine version of the SDS for recreational users. Considering that ketamine use is linked to young people and its strong potential for causing serious impairment, a cut-off of 3 is proposed as indicative of dependence.

Erectile Dysfunction among People Who Use Ketamine and Poly-Drugs

ABSTRACTDespite the rise in recreational use of ketamine in Malaysia, there have been no studies of users or of the health-related consequences they face. This study was initiated to examine ketamine use and its health consequences. A structured questionnaire was used to elicit information. A final sample of 127 males was divided into persons who used only ketamine and those who were poly-drug users. Each group was further divided into long-period and short-period users. Urine toxicology screening for ketamine and other illicit drugs commonly used in Malaysia was also done. Our findings corroborate those of earlier studies that link ketamine use to urological problems such as frequent urination, dysuria, incontinence, painful bladder, nocturia, and urinary urgency. A new finding in this study is the significant association between ketamine use and erectile dysfunction, such that higher odds of reporting erectile dysfunction were linked to long-period users. Our findings strengthen the case for early intervention, as ketamine users are drawn from young and unmarried male participants. The association of ketamine use with erectile dysfunction, if substantiated, will help physicians in their diagnosis of erectile dysfunction, particularly among youths.

Profiling the psychotic, depressive and anxiety symptoms in chronic ketamine users

ObjectiveAlthough concern about chronic ketamine abuse has grown, the characteristic symptomatology of chronic ketamine users has yet to be examined. This study aims to measure the psychotic, depressive and anxiety symptoms in chronic ketamine users. MethodsA group of chronic ketamine users in Guangzhou, China were evaluated. The socio-demographic and drug use characteristics of subjects were documented. Symptoms of psychosis, depression, anxiety were evaluated by the Positive and Negative Syndrome Scale (PANSS), Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI). The severity of the symptoms was identified by standard severity cutoffs. ResultsThe PANSS total score, positive symptom, negative symptom, general psychopathology subscale score were 45.3±8.4, 8.0±1.7, 13.2± 3.9 and 24.2± 4.9 respectively. BDI and BAI score was 13.1±6.5 and 15.7±9.6 respectively. 77.5% and 46.0% of the subjects showed moderate to severe depressive symptoms and anxiety symptoms respectively. The BDI score was positively correlated with ketamine use frequency. The BAI score was positively correlated with ketamine use frequency. ConclusionsDepressive symptoms were commonly presented in chronic ketamine users. The higher ketamine use frequency and dosage were associated with more severe depressive symptoms.

Determination of hair ketamine cut-off value from Hong Kong ketamine users by LC–MS/MS analysis

Ketamine is one of the most frequent abused drugs in Hong Kong and South-East Asia, and the cases of ketamine abused have been reported worldwide. Hair has been commonly used as a specimen for the proof of chronic drug abused because of its non-invasiveness and long detection windows. The determinations of ketamine in hair with varieties of state-of-the-art instruments and detection methods have been developed in the past decade; however, the cut-off value for ketamine abuser has not been developed according to the international guidelines. The aim of this study is to propose a cut-off value for ketamine in hair by analyzing ketamine and its metabolite norketamine by LC–MS/MS method in a population of ketamine users in Hong Kong. The limit of detection (LOD) and limit of quantification (LOQ) for ketamine and norketamine were 20pg/mg and 100pg/mg, respectively. From 977 ketamine abusers, the cut-off value for ketamine in hair was proposed to be 400pg/mg of hair. This proposed cut-off value is the concentration of hair ketamine when over 90% of samples are being detected with the presence of norketamine, which is a proof of ketamine abuse. This value could be applied as a screening or occupational cut-off for reference.

Neurocognitive Profiles of Methamphetamine Users: Comparison of Those With or Without Concomitant Ketamine Use

Objective: Methamphetamine (MAMP) and ketamine are neurotoxic drugs whose chronic use has been linked with a cognitive decline in some users. This paper aims to assess the possible effect of concomitant ketamine use on the neurocognitive performance of MAMP users. Methods: This study divides 42 MAMP users into MAMP users who use ketamine (MAMP+K, n = 16) and MAMP users who do not use ketamine (MAMP–K, n = 26). The performance of these two groups was compared using the Brief Assessment of Cognition in Schizophrenia (BACS), Conners’ Continuous Performance Tests (CPT), the Wisconsin Card Sorting Test (WCST), the Iowa Gambling Task (IGT), and the Barratt Impulsiveness Scale (BIS). Results: In comparison to the MAMP-K group, the MAMP+K group showed worse performances in verbal fluency, executive function and composite score in BACS; worse performances in total errors, perseverative errors, nonperseverative errors and conceptual level response in WCST; and greater levels of total scores and novelty-seeking in BIS. Neither the attention function evaluated with CPT nor the decision-making behavior evaluated with IGT was associated with previous ketamine use. Conclusion: This study detected worse executive function and higher impulsivity level among MAMP users with additional ketamine use versus their counterparts without ketamine use. Further studies with a longitudinal design and a large sample size are necessary to clarify the connection between cognitive deficits and concomitant use of MAMP and ketamine.

Relationship of serum levels of TNF-α, IL-6 and IL-18 and schizophrenia-like symptoms in chronic ketamine abusers

ObjectiveExposing to NMDAR receptor antagonists, such as ketamine, produces schizophrenia-like symptoms in humans and deteriorates symptoms in schizophrenia patients. Meanwhile, schizophrenia is associated with alterations of cytokines in the immune system. This study aims to examine the serum TNF-α, IL-6 and IL-18 levels in chronic human ketamine users as compared to healthy subjects. The correlations between the serum cytokines levels with the demographic, ketamine use characteristics and psychiatric symptoms were also assessed. Methods155 subjects who fulfilled the criteria of ketamine dependence and 80 healthy control subjects were recruited. Serum TNF-α, IL-6 and IL-18 levels were measured using an enzyme-linked immunosorbent assay (ELISA). The psychiatric symptoms of the ketamine abusers were assessed using the Positive and Negative Syndrome Scale (PANSS). ResultsSerum IL-6 and IL-18 levels were significantly higher, while serum TNF-α level was significantly lower among ketamine users than among healthy controls (p<0.05). Serum TNF-α levels showed a significant negative association with PANSS total score (r=−0.210, p<0.01) and negative subscore (r=−0.300, p<0.01). No significant association was found between PANSS score and serum levels of IL-6 and IL-18. ConclusionsSerum levels of TNF-α, IL-6 and IL-18 were altered in chronic ketamine abusers which may play a role in schizophrenia-like symptoms in chronic ketamine abusers.

Decreased thalamocortical connectivity in chronic ketamine users

Decreased thalamocortical connectivity in chronic ketamine users

MDMA, cannabis, and cocaine produce acute dissociative symptoms

Some drugs of abuse may produce dissociative symptoms, but this aspect has been understudied. We explored the dissociative potential of three recreational drugs (3,4-methylenedioxymethamphetamine (MDMA), cannabis, and cocaine) during intoxication and compared their effects to literature reports of dissociative states in various samples. Two placebo-controlled studies were conducted. In Study 1 (N=16), participants received single doses of 25, 50, and 100mg of MDMA, and placebo. In Study 2 (N=21), cannabis (THC 300µg/kg), cocaine (HCl 300mg), and placebo were administered. Dissociative symptoms as measured with the Clinician-Administered Dissociative States Scale (CADSS) significantly increased under the influence of MDMA and cannabis. To a lesser extent, this was also true for cocaine. Dissociative symptoms following MDMA and cannabis largely exceeded those observed in schizophrenia patients, were comparable with those observed in Special Forces soldiers undergoing survival training, but were lower compared with ketamine-induced dissociation. Cocaine produced dissociative symptoms that were comparable with those observed in schizophrenia patients, but markedly less than those in Special Forces soldiers and ketamine users. Thus, MDMA and cannabis can produce dissociative symptoms that resemble dissociative pathology. The study of drug induced dissociation is important, because it may shed light on the mechanisms involved in dissociative psychopathology.

Sleeping problems in Chinese illicit drug dependent subjects.

BackgroundIllicit drug use/dependence has been recognized as a major problem. Clinical studies demonstrate that poor sleep quality is associated with increased frequency of drug use and relapse. However, few studies have addressed the issue of sleep quality among illicit drug dependent subjects.MethodsThis cross-sectional study explored sleep quality in drug dependent subjects in China. We studied 2178 illicit drug dependent subjects from drug rehabilitation centres in Changsha and 2236 non-drug-using subjects, all of whom completed the self-report Pittsburgh Sleep Quality Index (PSQI).ResultsWe found that the prevalence of sleep disturbance was much higher in drug users (68.5%, PSQI >5; specifically, 80.24% in heroin users, 54.16% in methamphetamine users and 81.98% in ketamine users with PSQI >5) than non-users (26.4%, PSQI >5). Drug users had approximately twice the sleep latency than nondrug users (37.7 minutes V.S 18.4 minutes). Although drug users and non-users reported similar sleep duration (about 7.4 hours), drug users showed poorer subjective sleep quality and habitual sleep efficiency. They reported more sleep disturbance and need for sleep medications, more daytime dysfunction and poorer subjective sleep quality compared with nondrug users. The total PSQI score positively correlated with the duration of drug use (rp = 0.164, p < 0.001). We also found a link between sleep problems and cigarette smoking, alcohol drinking, and duration of drug use.ConclusionsPoor sleep quality is common among illicit drug dependent subjects. Long-term substance users had more sleep problems. Future research aiming at quantifying the benefits of treatment interventions should not neglect the influence of sleep problems. Gaining more insight into the impact of sleep quality on the addiction treatment could also help to target future intervention measures more effectively.

Psychiatric Morbidity in Ketamine Users Attending Counselling and Youth Outreach Services

ABSTRACTBackground: No study has examined ketamine users’ psychiatric morbidity using structured diagnostic instruments. The aim of this study was thus to determine the psychiatric comorbidity of community-based ketamine users using the Structured Clinical Interview for DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition), Axis I Disorders (SCID). Methods: A convenience sample of 200 frequent ketamine users was recruited from community organizations in Hong Kong. Participants were screened with the Severity of Dependence Scale (SDS), Beck Depression Inventory (BDI), Anxiety subscale of the Hospital Anxiety Depression Scale (HADSA), and SCID psychotic symptoms. Those who scored above the threshold (cutoff point of 8/9 on the BDI and 4/5 on HADSA) or displayed evidence of psychotic symptoms were referred for a structured clinical interview conducted by a psychiatrist. Results: One hundred and seventy participants scored above the cutoff point on 1 or more of the scales, and 115 participants attended the SCID interview. Fifty-one of these 115 participants received a psychiatric diagnosis of 1 or more comorbidities for the month preceding the interview. Mood disorders accounted for 80.4% of the diagnoses, anxiety disorders for 33.3%, and psychotic disorders for 7.8%. Conclusions: Female gender and history of psychiatric/psychological clinic attendance were significantly associated with comorbid psychiatric disorders, whereas ketamine dependence had a borderline association.

Ketamine users have high rates of psychosis and/or depression.

Ketamine has been linked to psychosis and used in the treatment of depression. However, no study has examined the prevalence of psychotic and depressive disorders in dependent ketamine users. This study aimed to examine the frequency of various psychopathologies among a series of patients seeking treatment for ketamine use in Hong Kong, China. The case records of 129 patients with a history of ketamine use receiving treatment at three substance use clinics between January 2008 and August 2012 were retrieved for data collection. Patients' demographic data, patterns of substance misuse, and comorbid psychiatric diagnoses were recorded and entered into analyses. The mean age of onset and length of ketamine use were 17.7 ± 4.4 and 8.7 ± 5.7 years, respectively. All patients were dependent on ketamine at the time of data collection. Multiple substance misuse was common. Eighty-four of the 129 (65.1%) patients were found to have comorbid psychiatric disorders, most commonly substance-induced psychotic disorder (31.8%) followed by depressive disorder (27.9%). Psychosis and/or depression were common in ketamine-dependent patients referred to a psychiatric substance use clinic. The findings provide evidence of an association between chronic ketamine use and the presence of psychosis and/or depression. The results raise the issue of safety when using ketamine in the long-term treatment of depression.

Preliminary analysis of positive and negative syndrome scale in ketamine-associated psychosis in comparison with schizophrenia

ObjectiveStudies of the effects of the N-methyl-d-aspartate (NMDA) glutamate receptor antagonist, ketamine, have suggested similarities to the symptoms of schizophrenia. Our primary goal was to evaluate the dimensions of the Positive and Negative Syndrome Scale (PANSS) in ketamine users (acute and chronic) compared to schizophrenia patients (early and chronic stages). MethodWe conducted exploratory factor analysis for the PANSS from four groups: 135 healthy subject administrated ketamine or saline, 187 inpatients of ketamine abuse; 154 inpatients of early course schizophrenia and 522 inpatients of chronic schizophrenia. Principal component factor analyses were conducted to identify the factor structure of the PANSS. ResultsFactor analysis yielded five factors for each group: positive, negative, cognitive, depressed, excitement or dissociation symptoms. The symptom dimensions in two schizophrenia groups were consistent with the established five-factor model (Wallwork et al., 2012). The factor structures across four groups were similar, with 19 of 30 symptoms loading on the same factor in at least 3 of 4 groups. The factors in the chronic ketamine group were more similar to the factors in the two schizophrenia groups rather than to the factors in the acute ketamine group. Symptom severities were significantly different across the groups (Kruskal–Wallis χ2(4) = 540.6, p < 0.0001). Symptoms in the two ketamine groups were milder than in the two schizophrenia groups (Cohen's d = 0.7). ConclusionOur results provide the evidence of similarity in symptom dimensions between ketamine psychosis and schizophrenia psychosis. The interpretations should be cautious because of potential confounding factors.

Comparison of impulsivity and decision making in ketamine, opioid and non-drug users

Comparison of impulsivity and decision making in ketamine, opioid and non-drug users

Long-Term Heavy Ketamine Use is Associated with Spatial Memory Impairment and Altered Hippocampal Activation

Ketamine, a non-competitive N-methyl-d-aspartate receptor antagonist, is rising in popularity as a drug of abuse. Preliminary evidence suggests that chronic, heavy ketamine use may have profound effects on spatial memory but the mechanism of these deficits is as yet unclear. This study aimed to examine the neural mechanism by which heavy ketamine use impairs spatial memory processing. In a sample of 11 frequent ketamine users and 15 poly-drug controls, matched for IQ, age, years in education. We used fMRI utilizing an ROI approach to examine the neural activity of three regions known to support successful navigation; the hippocampus, parahippocampal gyrus, and the caudate nucleus during a virtual reality task of spatial memory. Frequent ketamine users displayed spatial memory deficits, accompanied by and related to, reduced activation in both the right hippocampus and left parahippocampal gyrus during navigation from memory, and in the left caudate during memory updating, compared to controls. Ketamine users also exhibited schizotypal and dissociative symptoms that were related to hippocampal activation. Impairments in spatial memory observed in ketamine users are related to changes in medial temporal lobe activation. Disrupted medial temporal lobe function may be a consequence of chronic ketamine abuse and may relate to schizophrenia-like symptomatology observed in ketamine users.

Chronic administration of ketamine mimics the perturbed sense of body ownership associated with schizophrenia.

Subanaesthetic ketamine infusion in healthy volunteers induces experiences redolent of early psychosis, including changes in the experience of one's own body. It is not clear, however, whether repeated self-administration of ketamine has a sustained effect on body representation that is comparable to that found during acute administration. We sought to establish whether chronic ketamine use resulted in disturbances to sense of body ownership. Following on from our work on the effects of acute ketamine infusion, we used the rubber hand illusion (RHI) to experimentally manipulate the sense of body ownership in chronic ketamine users, compared to healthy controls. Chronic ketamine users experienced the RHI more strongly and reported more body-image aberrations, even though they had not recently taken the drug. These findings suggest that the chronic ketamine model for psychosis models more long-lasting changes in sense of ownership, perhaps more akin to schizophrenia.

Gender differences in subjective discontinuation symptoms associated with ketamine use.

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.

SY23-4 * BRAIN IMAGING STUDY ON KETAMINE ABUSERS

Ketamine had been used as an anesthetic for a long time. In recent years, unfortunately, ketamine has become an abusive drug in many parts of the world including Taiwan. However, there are only few neuroimaging studies on possible damages induced by ketamine in the brains. A recent study reported brain damages on chronic ketamine abusers by MRI study and showed atrophy over several regions. Also white matter changes were found in bilateral frontal and left temporo-parietal cortices. Another study was conducted on healthy subjects received ketamine challenge and revealed decreases brain functional connectivity of Default Mode Network. Despite some progress in identifying changes in behavior and brain function following heavy ketamine use; our current understanding of the effects of ketamine on the brain is poor. Specifically, we conduct a two-year study with 30 ketamine users being recruited. We will characterize behavioral performance, changes of brain structural and activities in ketamine users, as compared the healthy controls. The potential findings will extend the literature in addiction neuroscience and provide critical information facilitating research and treatment of ketamine misuse.

Self-reported prevalence of dependence of MDMA compared to cocaine, mephedrone and ketamine among a sample of recreational poly-drug users

BackgroundEvidence regarding MDMA (ecstasy) dependence and the most suitable criteria for its assessment are controversial. This study aimed to assess the prevalence of last year symptoms of dependence upon MDMA compared to cocaine, mephedrone and ketamine among a large global non-treatment seeking sample. MethodsA cross-sectional anonymous online survey was promoted by a UK-based dance music website between 15 November 2010 and 1 January 2011. Endorsement of DSM-IV (Diagnostic and Statistical Manual of Mental Disorders) dependence criteria was sought from all last year users of MDMA, cocaine, mephedrone and ketamine. Reporting ≥3 dependence symptoms was indicative of dependence. Logistic regression models with Generalized Estimating Equations were used to compare dependence symptoms between groups. ResultsMDMA users were more likely to report ≥3 DSM-IV dependence symptoms compared to users of cocaine (odds ratio OR 0.81, 95% confidence interval CI 0.71–0.93), mephedrone (OR 0.91, 95%CI 0.78–1.06) and ketamine (OR 0.52, 95%CI 0.44–0.62) (p<0.001). MDMA users were less likely to report desire to use less or get help compared to users of other substances (p<0.001). MDMA got the highest rating of pleasurable high (mean 8.2±1.7) and lowest rating for risk of harm (mean 2.7±2.4). ConclusionsOur results highlight the self-reported dependence potential of MDMA but low desire to use less or get help. MDMA's pleasurable effects may compensate for drug-related problems and, therefore, DSM-IV criteria may not be suitable for assessing MDMA dependence. Further research is needed on the ability of DSM-V to assess MDMA dependence.

Serum brain-derived neurotrophic factor and nerve growth factor decreased in chronic ketamine abusers

AimsThis study investigated the serum levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in a group of chronic ketamine abusers in comparison to healthy controls. The correlations between the serum BDNF, NGF level with the subjects’ demographic, pattern of ketamine use were also examined. Methods93 subjects who met the criteria of ketamine dependence and 39 healthy subjects were recruited. Serum BDNF and NGF levels were assayed by enzyme-linked immunosorbent assay (ELISA). Psychopathological symptoms were assessed using Positive and Negative Syndrome Scale (PANSS), Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI). ResultsBoth serum levels of BDNF and NGF were significant lower in the ketamine users compared to the healthy control subjects (9.50±6.68 versus 14.37±6.07ng/ml, p=0.019 for BDNF; 1.93±0.80 versus 2.60±1.07ng/ml, p=0.011 for NGF). BDNF level was negatively associated with current frequency of ketamine use (r=−0.209, p=0.045). ConclusionsBoth BDNF and NGF serum concentrations were significantly lower among chronic ketamine users than among health controls.