Ketamine Users Research Articles

The prevalence and natural history of urinary symptoms among recreational ketamine users

The prevalence and natural history of urinary symptoms among recreational ketamine users

P.6.c.007 Associative blocking to reward-predicting cues is attenuated in ketamine users but can be modulated by images associated with drug use

P.6.c.007 Associative blocking to reward-predicting cues is attenuated in ketamine users but can be modulated by images associated with drug use

Psychological effects of ketamine: a research note

PurposeKetamine intoxication has been mooted as a model of some of the signs and symptoms of psychosis. However, little research has focused on the self‐report experience of ketamine users. The purpose of the current study is to quantify (the frequency of occurrence of) ketamine induced phenomenology in recreational users. The paper also seeks to meaningfully group these experiences into facets and their principal components.Design/methodology/approachRespondents completed a checklist of experiences, the Ketamine Experiences Questionnaire (KEQ). Two samples were recruited via opportunity and snowball sampling one in 2009 (n=52) and one in 2010/11 (n=35).FindingsThe “Q‐sort” and principal component analysis (PCA) indicate that there are two factors, factor one representing aversive ketamine experiences (accounting for 48.2 per cent of the variance) and factor two representing appetitive ketamine experiences (accounting for 20.1 per cent of the variance). Ketamine induces a raft of appetitive, aversive and transcendental experiences many of which are illustrated. The data suggest that a decision about whether to continue using ketamine (and if so, how often) depends in part on an intuitive cost‐benefit analysis of the phenomenology that it induces.Research limitations/implicationsThere are some notable limitations to the current study; the small sample size to variable ratio necessitated a “Q‐sort” before PCA; the sampling procedure prohibited the generation of a representative sample; and there were no means of independently verifying ketamine use.Originality/valueThis study represents a novel exploration into ketamine phenomenology and the principal components of these experiences.

THE PREVALENCE AND NATURAL HISTORY OF URINARY SYMPTOMS AMONG RECREATIONAL KETAMINE USERS

Study Type – Symptom prevalence (prospective cohort) Level of Evidence 1b What's known on the subject? and What does the study add? Case series have described lower urinary tract symptoms associated with ketamine use including severe pain, frequency, haematuria and dysuria. Little is known regarding the frequency of symptoms, relationship of symptoms with dose and frequency of use and natural history of symptoms once the ketamine user has stopped. This study describes the prevalence of ketamine use in a population of recreational drug users in a dance music setting. It shows a dose–frequency relationship with ketamine use. It shows that urinary symptoms associated with recreational ketamine use may lead to a considerable demand on health resources in the primary-, secondary- and emergency-care settings. It shows that symptoms may improve once ketamine use is decreased. OBJECTIVE • To investigate the prevalence and natural history of urinary symptoms in a cohort of recreational ketamine users. PATIENTS AND METHODS • A purposeful sampling technique was used. • Between November 2009 and January 2010 participants were invited to undertake an on-line questionnaire promoted by a national dance music magazine and website. • Data regarding demographics and illicit drug-use were collected. • Among respondents reporting recent ketamine use, additional information detailing their ketamine use, experience of urinary symptoms and use of related healthcare services was obtained. RESULTS • In all, 3806 surveys were completed, of which 1285 (33.8%) participants reported ketamine use within the last year. • Of the ketamine users, 17% were found to be dependent on the drug; 26.6% (340) of recent ketamine users reported experiencing urinary symptoms. • Urinary symptoms were significantly related to both dose of ketamine used and frequency of ketamine use. • Of 251 users reporting their experience of symptoms over time in relationship to their use of ketamine, 51% reported improvement in urinary symptoms upon cessation of use with only eight (3.8%) reporting deterioration after stopping use. CONCLUSIONS • Urinary tract symptoms are reported in over a quarter of regular ketamine users. • A dose and frequency response relationship has been shown between ketamine use and urinary symptoms. • Both users and primary-care providers need to be educated about urinary symptoms that may arise in ketamine users. A multi-disciplinary approach promoting harm reduction, cessation and early referral is needed to manage individuals with ketamine-associated urinary tract symptoms to avoid progression to severe and irreversible urological pathologies.

Associative blocking to reward-predicting cues is attenuated in ketamine users but can be modulated by images associated with drug use

Blocking is an associative learning process that is attenuated in schizophrenia, can be modulated by cue salience and is accompanied by changes in selective attention. Repeated exposure to ketamine can model aspects of schizophrenia, and frequent users selectively attend to images of the drug. This study aimed to establish whether (1) ketamine users show attenuated blocking to reward-predicting cues and (2) drug cues can modulate blocking and cause overshadowing of neutral cues that are equally predictive of reward in these individuals. Ketamine users (n = 18) and polydrug controls (n = 16) were assessed on the Drug Cue Reward Prediction Error Task, which indexes blocking and overshadowing to neutral and drug-related cues following Pavlovian reward conditioning. Schizotypy, depression, drug history and ketamine dependence were also assessed. Compared to controls, ketamine users showed elevated delusional, schizotypal and depressive symptoms, and a reduction in blocking as evidenced by higher accuracy to blocked cues. Drug-related cues were resistant to blocking and seen as more important for earning money by ketamine users compared to controls. Both groups showed overshadowing of neutral cues by drug cues, and ketamine users gave both of these cues higher importance ratings than controls. These findings provide the first evidence that (1) glutamatergic perturbation is linked to a reduction in blocking and (2) blocking can be modulated by the presence of drug-related cues. The ability of drug cues to bias selective learning about 'alternative rewards' has implications for contingency management based addiction treatments.

Individual and peer factors associated with ketamine use among adolescents in Taiwan

The aim of this cross-sectional study was to examine the individual (demographic characteristics, substance-using behaviors, emotional status, and negative outcome expectancy) and peer factors associated with ketamine use in Taiwanese adolescents. A total of 9,860 adolescents completed the self-report questionnaires without omission. Demographic characteristics, substance-using behaviors, emotional status, negative outcome expectancy, and peer factors were compared between the ketamine users and non-users using the Mann-Whitney U test and the Chi-square test, and then significant factors were further selected for stepwise logistic regression analysis to examine the associated factors of ketamine use. Sixty-nine (0.7%) participants reported having used ketamine in the past year. The results of logistic regression analysis indicated that ketamine users were more likely to use marijuana, smoke cigarettes, have peers using illicit drugs, and have a lower level of negative outcome expectancy regarding using ketamine than ketamine non-users. The associated factors found in this study should be taken into consideration when developing prevention and intervention programs for ketamine use in adolescents.

Alterations in regional homogeneity of resting-state brain activity in ketamine addicts

Ketamine is a non-competitive anatognist of the N-methyl-d-aspartate (NMDA) receptor commonly used as an anesthetic and analgesic. In sub-anesthetic doses, it can induce temporary psychotic symptoms and has served as a pharmacological model for schizophrenia. While its acute effects on brain and behavior have been studied, the effects of long-term exposure to ketamine on brain activity have been largely unexplored. In this study, we aimed to examine such effects on spontaneous brain dynamics measure using resting-state functional magnetic resonance imaging (fMRI). Forty-one patients with ketamine dependence and forty-four healthy control subjects were imaged with BOLD fMRI using a 3.0-Tesla Siemens scanner at the Magnetic Resonance Center of Hunan Provincial People's Hospital, analyzed with the regional homogeneity (ReHo) method. Compared with healthy controls, decreased ReHo was found in ketamine users in the right anterior cingulate cortex and increased ReHo was found in left precentral frontal gyrus (p<0.05, cluster-level corrected). We also observed negative correlations between increased ReHo in precentral frontal gyrus and estimated total lifetime ketamine consumption and ketamine craving levels. To our knowledge, this is the first study the long-term effects of ketamine exposure on brain functional activity. Our findings indicate that ketamine dependence is associated with alterations in the functional connectivity of medial and lateral prefrontal cortices.

Subchronic ketamine treatment leads to permanent changes in EEG, cognition and the astrocytic glutamate transporter EAAT2 in mice

Ketamine is an NMDA receptor antagonist with psychotomimetic, dissociative, amnestic and euphoric effects. When chronically abused, ketamine users display deficits in cognition and information processing, even following long-term abstinence from the drug. While animal studies have shown evidence of behavioral changes and cognitive deficits that mimic those seen in humans within the period immediately following subchronic ketamine, a few animal studies have assessed long-term changes following cessation of ketamine exposure. To this end, the present study assessed event related potentials (ERPs) and EEG oscillations in mice exposed to subchronic ketamine following a 6month period of abstinence from the drug. Ketamine-treated mice showed no change in P20, but did show marked reductions in amplitude of the later N40 and P80 components, consistent with previous studies of acute ketamine exposure. Additionally, ketamine-treated animals showed a significant reduction in stimulus evoked theta oscillations. To assess the functional significance of these changes, mice were also assessed on a series of behavioral and cognitive tests, including progressive ratio (motivation), extinction (behavioral flexibility) and win-shift radial maze (spatial memory). Subchronic ketamine produced marked disruptions in reversal learning and spatial memory. Analysis of brains from ketamine-treated mice failed to show evidence of neuronal degeneration as determined by NueN immunohistochemistry, but did show increased astrocyte proliferation and decreased expression of the glial specific glutamate transporter, GLT-1. These results strongly suggest: 1) that subchronic ketamine induces significant changes in brain function that long exceed exposure to the drug; 2) that ketamine exposure in mice induces lasting cognitive impairments closely resembling those observed in human ketamine abusers; 3) that ERP and EEG measures are highly sensitive to alterations in brain function associated with reduced cognitive function; and 4) that the brain changes induced by chronic ketamine treatment are suggestive of long-term adaptive or plastic, rather than degenerative, changes.

Neurocognitive Function and Schizophrenia-Proneness in Individuals Dependent on Ketamine, on High Potency Cannabis (‘Skunk’) or on Cocaine

Ketamine, psychostimulants and cannabis have all been associated with psychotic phenomena but no study has directly compared users of these drugs. The aim of this study was to assess schizophrenia proneness and neurocognitive function in individuals dependent upon ketamine, cannabis and cocaine. 130 volunteers - 29 'skunk' users, 22 cocaine users, 21 ketamine users, along with 28 'recreational' poly-drug users and 30 drug-naïve controls - were assessed on the Schizophrenia Proneness Instrument, Adult version (SPI-A). They were specifically asked to rate symptoms when not under the acute influence of a psychoactive drug. Ketamine and skunk users manifested the greatest attentional and cognitive disturbances. The symptom profile of the dependent ketamine users was very similar to that of prodromal individuals who transitioned to psychosis. Given the recent rapid rise in use of high potency cannabis and of ketamine, these findings are important and clinicians should be careful to rule out the effects of persistent drug use, especially in users of ketamine or skunk, when assessing an individual's risk of psychosis. A longitudinal study is needed to differentiate which basic symptoms persist following abstention from ketamine and skunk.

The prevalence and natural history of urinary symptoms among recreational ketamine users

Study Type--Symptom prevalence (prospective cohort) Level of Evidence 1b. What's known on the subject? and What does the study add? Case series have described lower urinary tract symptoms associated with ketamine use including severe pain, frequency, haematuria and dysuria. Little is known regarding the frequency of symptoms, relationship of symptoms with dose and frequency of use and natural history of symptoms once the ketamine user has stopped. This study describes the prevalence of ketamine use in a population of recreational drug users in a dance music setting. It shows a dose-frequency relationship with ketamine use. It shows that urinary symptoms associated with recreational ketamine use may lead to a considerable demand on health resources in the primary-, secondary- and emergency-care settings. It shows that symptoms may improve once ketamine use is decreased. • To investigate the prevalence and natural history of urinary symptoms in a cohort of recreational ketamine users. • A purposeful sampling technique was used. • Between November 2009 and January 2010 participants were invited to undertake an on-line questionnaire promoted by a national dance music magazine and website. • Data regarding demographics and illicit drug-use were collected. • Among respondents reporting recent ketamine use, additional information detailing their ketamine use, experience of urinary symptoms and use of related healthcare services was obtained. • In all, 3806 surveys were completed, of which 1285 (33.8%) participants reported ketamine use within the last year. • Of the ketamine users, 17% were found to be dependent on the drug; 26.6% (340) of recent ketamine users reported experiencing urinary symptoms. • Urinary symptoms were significantly related to both dose of ketamine used and frequency of ketamine use. • Of 251 users reporting their experience of symptoms over time in relationship to their use of ketamine, 51% reported improvement in urinary symptoms upon cessation of use with only eight (3.8%) reporting deterioration after stopping use. • Urinary tract symptoms are reported in over a quarter of regular ketamine users. • A dose and frequency response relationship has been shown between ketamine use and urinary symptoms. • Both users and primary-care providers need to be educated about urinary symptoms that may arise in ketamine users. A multi-disciplinary approach promoting harm reduction, cessation and early referral is needed to manage individuals with ketamine-associated urinary tract symptoms to avoid progression to severe and irreversible urological pathologies.

Anomalous bodily-self experiences among recreational ketamine users

Introduction. Out-of-body experiences present a unique paradigm to investigate cognitive and neural mechanisms of bodily-self processes and their disorders. Previous work on out-of-body experiences associated with sleep paralysis supported a model in which illusory movement experiences reflect disrupted bodily-self integration generating anomalous vestibular and motor sensations. Further disintegration and progression of the experience may then give rise to out-of-body feelings, which in turn may instigate out-of-body autoscopy. Methods. The current study assesses the disintegration model through analyses of out-of-body experiences reports from an online survey of individuals reporting recreational ketamine use (n=128) and cross-validation in a sample of nonketamine polydrug users (n=64). Path analyses using intensity and frequency measures of anomalous experiences assess the fit of seven competing models. Results. The disintegration model (illusory movement → out-of-body feelings → out-of-body autoscopy) emerged as the best fitting model overall and results support full mediation of the relation between illusory movement experiences and out-of-body autoscopy by out-of-body feelings. Moreover, lifetime measures of ketamine use predicted the frequency of illusory movement experiences. Conclusions. The results corroborate this structural model of out-of-body phenomena and encourage a framework for future studies into aetiological mechanisms of out-of-body experiences to include neurochemical systems.

Prevalence and perceptions of ketamine use among Danish clubbers: A mixed-method study

Aims This article describes the prevalence of ketamine use among Danish recreational drug users and provides a contextual understanding of ketamine use within this group. Methods and Data The analysis is based on a mixed-methods night club study combining a survey among guests in night clubs (N=1,632) with qualitative interviews (9 focus group interviews, 6 double interviews, 7 individual interviews; 53 clubbers in total). Results 10% of the clubbers have tried ketamine (lifetime use). The ketamine users have also tried a range of other drugs. When taken in club settings, ketamine is often part of a polydrug repertoire. When used in private settings, ketamine is often taken alone to explore its hallucinogenic effects. The users are aware of the potency of the drug, but do not pay attention to long-term negative effects of ketamine use. Conclusion Ketamine users predominantly prefer to use ketamine in private settings. This can be viewed as a strategy for risk management, but also as a way of optimising the combination of drug – place – social – body, thereby creating a drug experience that is not possible in public settings.

Cystitis and ketamine-associated bladder dysfunction

ObjectivesTo analyze the prevalence of lower urinary tract symptoms (LUTS) in recreational ketamine users and evaluate its relationship with the consumption pattern. Material and methodsEvaluation of 13 ketamine users. The presence of LUTS, gross hematuria and lumbar spine pain was analyzed. The ketamine usage pattern was recorded: initiation, administration route, dose in the last month, and frequency of usage. ResultsSix patients (46%) reported LUTS, with daily mean micturations every 42min and nighttime of 3 episodes, with dysuria (100%), urgency (100%), incontinence (20%), decreased flow (80%), hypogastric or perineal pain (80%), gross hematuria (80%) and bilateral lumbar spine pain (40%). Symptomatic patients described a mean intake of inhaled ketamine of 3g/day (SD 2), 80% with a daily frequency and the asymptomatic ones of 1.03g/day (SD 0.92) limited to weekends. The mean consumption time to the appearance of the symptoms was 31 months (SD 16.29). Intensity of the symptoms was related with the ketamine dose and improved on increasing water intake. ConclusionsThere seems to be a relationship between the picture with the dose and frequency of consumption, there being factors that reinforce the hypothesis that this action of the drug is due to the harmful effect on the urothelium. The process to identify it on time should be known, since the only known effective measure is to stop the consumption in the initial phases.

Ketamine-snorting associated cystitis

Ketamine hydrochloride, commonly used as a pediatric anesthetic agent, is an N-methyl-D-aspartic (NMDA) acid receptor antagonist with rapid onset and short duration of action. It produces a cataleptic-like state where the patient is dissociated from the surrounding environment by direct action on the cortex and limbic system. It has emerged as an increasingly popular choice among young drug users, especially within dance club venues. Cases of bladder dysfunction among recreational ketamine users were reported since Shahani et al first reported nine cases of ketamine-associated ulcerative cystitis in 2007. We report on four patients who had history of ketamine abuse, presenting with dysuria, fluctuating lower urinary tract symptoms (LUTS), lower abdominal or perineal pain, and impaired functional bladder capacities. Urinalysis showed pyuria and microhematuria. Urine culture was sterile. Bladder ulceration with severe diffuse hemorrhage and low bladder capacity were noted under anesthetized cystoscopic examination. Transurethral bladder mucosa biopsy was consistent with chronic cystitis. Cessation of ketamine abuse was the milestone of treatment, followed by the administration of mucosal protective agents, such as pentosan polysulphate or hyaluronic acid. Suprapubic pain was improved in three patients during follow-up. However, the outcome of treatment depends on the severity of the disease process, similar to that of interstitial cystitis (IC).

Cistitis y disfunción vesical asociada al consumo de ketamina

Objectives To analyze the prevalence of lower urinary tract symptoms (LUTS) in recreational ketamine users and evaluate its relationship with the consumption pattern. Material and methods Evaluation of 13 ketamine users. The presence of LUTS, gross hematuria and lumbar spine pain was analyzed. The ketamine usage pattern was recorded: initiation, administration route, dose in the last month and frequency of usage. Results Six patients (46%) reported LUTS, with daily mean micturations every 42 minutes and nighttime of 3 episodes, with dysuria (100%), urgency (100%), incontinence (20%), decreased flow (80%), hypogastric or perineal pain (80%), gross hematuria (80%) and bilateral lumbar spine pain (40%). Symptomatic patients described a mean intake of inhaled ketamine of 3 g/day (SD 2), 80% with a daily frequency and the asymptomatic ones of 1.03 g/day (SD 0.92) limited to weekends. The mean consumption time to the appearance of the symptoms was 31 months (SD 16.29). Intensity of the symptoms was related with the ketamine dose and improved on increasing water intake. Conclusions There seems to be a relationship between the picture with the dose and frequency of consumption, there being factors that reinforce the hypothesis that this action of the drug is due to the harmful effect on the urothelium. The process to identify it on time should be known, since the only known effective measure is to stop the consumption in the initial phases.

Downregulation in the human and mice cerebella after ketamine versus ketamine plus ethanol treatment

To study the deleterious effects of ketamine and the potential interaction effects between ethanol and ketamine on the cerebellum, functional magnetic resonance imaging (fMRI) tests were performed on the habitual ketamine users (n = 3) when they flexed and extended their upper limbs. Another fMRI test was performed on the same participants in which they consumed alcohol (12%, 200 mL) 1 h before the test. Downregulation on the activity of cerebellum was observed and the level of activation in the cerebellum decreased dramatically in habitual ketamine users with alcohol consumption before the test. Further studies were performed by using male ICR mice receiving treatment of ketamine only [30 mg kg(-1) intraperitoneally (i.p.)] or ethanol only everyday (0.5 mL 12% orally) and those with coadministration of the above dosages of ketamine and ethanol for 3 months. Fewer Purkinje cells were observed in the cerebellar sections of ketamine treated mice under silver staining. For TUNEL test, a significant increase in the apoptotic cells were observed in the cerebella of the ketamine treated mice (P = 0.016) and of those with co-administration of ketamine and ethanol (P < 0.001), when compared with the control. A statistical significance (P < 0.001) in two-way ANOVA test indicated that there might be an interactive mechanism between ethanol and ketamine acting on the cerebellum.

Lower Urinary Tract Changes in Young Adults Using Ketamine

We identified the profile of lower urinary tract changes in ketamine users in the community. In addition, we identified the relative risks of dose, frequency of ingestion and duration of ketamine use for changes in lower urinary tract function. A mobile medical assessment service was established at specific youth centers, and subjects who were known to social workers and who had a history of ketamine use were invited to participate in health screening. Lower urinary tract function was evaluated using the Pelvic Pain, Urgency and Frequency questionnaire, and uroflowmetry and ultrasonography. Use of ketamine more than 3 times weekly was significantly associated with lower voided volumes. Pelvic Pain, Urgency and Frequency questionnaire scores were significantly higher for ketamine use for more than 24 months compared to use for short durations (7.82 vs 6.00). The scores on the symptom and bother subscales of the Pelvic Pain, Urgency and Frequency questionnaire decreased progressively with increased duration of abstinence. For individuals after 1 year of abstinence the Pelvic Pain, Urgency and Frequency questionnaire scores were significantly lower and voided volumes were higher than those for active users. Ketamine users with at least a 2-year habit of 3 or more hits per week have altered bladder function that can be recognized and that causes bother. These early functional changes have the potential to normalize after 1 year of ketamine abstinence. This study provides a basis for the development of health promotion material that can be used in the community by welfare workers seeking to encourage drug cessation.

To use or not to use: an update on licit and illicit ketamine use

Ketamine, a derivative of phencyclidine that was developed in the 1960s, is an anesthetic and analgesic with hallucinogenic effects. In this paper, the pharmacological and toxicological effects of ketamine are briefly reviewed. Ketamine possesses a wide safety margin but such a therapeutic benefit is somewhat offset by its emergence phenomenon (mind-body dissociation and delirium) and hallucinogenic effects. The increasing abuse of ketamine, initially predominantly in recreational scenes to experience a “k-hole” and other hallucinatory effects but more recently also as a drug abused during the workday or at home, has further pushed governments to confine its usage in many countries. Recently, urinary tract dysfunction has been associated with long-term ketamine use. In some long-term ketamine users, such damage can be irreversible and could result in renal failure and dialysis. Although ketamine has not yet been scheduled in the United Nations Conventions, previous studies using different assessment parameters to score the overall harms of drugs indicated that ketamine may cause more harm than some of the United Nations scheduled drugs. Some countries in Southeast and East Asia have reported an escalating situation of ketamine abuse. Dependence, lower urinary tract dysfunction, and sexual impulse or violence were the most notable among the ketamine-associated symptoms in these countries. These results implied that the danger of ketamine may have been underestimated previously. Therefore, the severity levels of the ketamine-associated problems should be scrutinized more carefully and objectively. To prevent ketamine from being improperly used and evolving into an epidemic, a thorough survey on the prevalence and characteristics of illicit ketamine use is imperative so that suitable policy and measures can be taken. On the other hand, recent findings that ketamine could be useful for treating major depressive disorder has given this old drug a new impetus. If ketamine is indeed a remedy for treating depression, more research on the risks and benefits of its clinical use will be indispensable.

Recreational ketamine: from pleasure to pain

Ketamine has become increasingly recognized as a drug of recreational use. Individuals using significant amounts have developed symptoms including a small painful bladder, ureteric obstruction, papillary necrosis and hepatic dysfunction. The present paper examines the current literature on the relationship between ketamine use and these symptoms. Our own clinical experience and the data available clarify the causal relationship, and further data help to elucidate the mechanism of damage. On the basis of continued work and development with patients who are ketamine users we suggest an assessment and treatment regime that includes cessation of ketamine use and adequate analgesia to overcome symptoms. In conclusion, it is important for medical practitioners who encounter patients with these symptoms to ask about recreational drug use. Ketamine remains a safe and effective drug to use under appropriate medical supervision. Patients identified as suffering from this syndrome will need to be referred to a urological unit with an interest in the treatment of the condition.

Chronic ketamine use increases serum levels of brain-derived neurotrophic factor

Ketamine is a non-competitive N-methyl-D: -aspartate (NMDA) receptor antagonist which interferes with the action of excitatory amino acids (EAAs) including glutamate and aspartate. The use of ketamine at subanaesthetic doses has increased because of its psychotomimetic properties. However, long-term ketamine abuse may interfere with memory processes and inhibit the induction of long-term potentiation (LTP) in the hippocampus, an effect probably mediated by its NMDA antagonist action. Neurotrophins such as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) serve as survival factors for selected populations of central nervous system neurons, including cholinergic and dopaminergic neurons. In addition, neurotrophins, particularly BDNF, may regulate LTP in the hippocampus and influence synaptic plasticity. The purpose of this study was to test the hypothesis that ketamine use in humans is associated with altered serum levels of neurotrophins. We measured by enzyme-linked immunosorbent assay the NGF and BDNF serum levels in two groups of subjects: frequent ketamine users and healthy subjects. Our data show that BDNF serum levels were increased in chronic ketamine users as compared to healthy subjects, while NGF levels were not affected by ketamine use. These findings suggest that chronic ketamine intake is associated with increases in BDNF serum levels in humans. Other studies are needed to explore the pharmacological and molecular mechanism by which ketamine, and/or other NMDA antagonists, may induce modification in the production and utilization of BDNF and alter normal brain function.