Herbal High: Substance-Induced Psychosis after Consumption of Seeds of the Hawaiian Baby Woodrose.

Seeds of the Hawaiian Baby Woodrose (HBWR, Argyreia nervosa) are known as "legal or herbal highs" and can be easily purchased online in Germany. They contain various ergot alkaloids, including lysergic acid amide (LSA), which is chemically related to lysergic acid diethylamide (LSD). Pharmacological data are limited but suggest that LSA-concentration in HBWR seeds is highly variable, and that adverse psychiatric and somatic effects are not related to LSA-dosage. Anecdotal, mostly cross-sectional clinical case reports describe spontaneous remission of intoxication-related somatic and psychiatric symptoms as well as intoxication-related death. Treatment recommendations for LSA-induced psychiatric syndromes are not available. We report here on the clinical course and treatment of a drug-induced psychosis after consumption of HBWR seeds. The adolescent had consumed HBWR seeds once before without suffering any negative effects.

How preclinical studies have influenced novel psychoactive substance legislation in the UK and Europe.

Novel psychoactive substances (NPS) are new drugs of abuse. Over the last 10 years 50-100 new NPS have been detected for the first time each year. This has led to numerous deaths and challenges to healthcare providers and law-makers worldwide. We review preclinical studies of NPS and discuss how these studies have influenced legislative decisions. We focus on the UK legal system but include experiences from Europe. We reviewed manuscripts from 2008-2019 and have summarised the in vitro and in vivo data on NPS, highlighting how these studies define pharmacological mechanisms and how they might predict harm in humans. We found that only a small percentage of NPS have been examined in preclinical studies. Most preclinical studies of NPS focus on basic pharmacological mechanisms (46% of studies reviewed) and/or addictive liability (32%) rather than toxicity and harm (24%). Very few preclinical studies into NPS include data from chronic dosing schedules (9%) or female rodents (4%). We conclude that preclinical studies can predict harm to humans, but most of the predictions are based on basic pharmacology rather than demonstrated toxicity. Some of these studies have been used to make changes to the law in the UK and Europe and perhaps, because of the paucity of toxicology data, most NPS have been placed in the highly dangerous schedule 1 or Class A category in the UK. We suggest that in silico studies and high throughput toxicology screens might be the most economical way forward to rapidly screen the health harms of NPS.

An international survey on the awareness, use, preference, and health perception of novel psychoactive substances (NPS).

OBJECTIVE: This survey investigated the level of public awareness, preference, and motivation of novel psychoactive substances (NPS) use as well as knowledge of potential associated health risks. METHODS: A Bristol Online Survey was advertised through social media and a drug forum "Bluelight" between January 7 and February 7, 2015. RESULTS: Responses were received from 17 countries, mainly from Europe. Most responses (83%) came from university educated students. Two-thirds (65%) of the 168 respondents were aware of NPS. Awareness was significantly increased in those with bisexual or homosexual orientation (p < .05) and those in employment (p < .05). Fourteen percent of the 168 respondents were users of NPS, and use was significantly affected by age and employment (p < .01) but unaffected by level of education (p > .05). Nearly half of the NPS users perceived NPS to carry either a low risk to health (20%) or did not know whether or not they posed a health risk (29%). CONCLUSIONS: These survey data indicate that awareness of NPS and, importantly, perception of the potential health risks associated with NPS use is lacking. NPS awareness and use is higher in those in employment but is unaffected by level of education. This highlights the need for targeted drugs education intervention by policy-makers in schools and universities.

[Psychoactive effects of 'legal high': About lysergic acid amide (LSA)]. / Effets psychoactifs des « legal high ¼ : à propos de l'acide lysergique amide (LSA).

Lysergic acid amide (LSA) is a natural psychoactive substance consumed as a psychedelic drug. In 2016, 4 cases were reported to the Toulouse Addictovigilance Centre, resulting in unintended psychic effects and led to a hospitalisation in 2 cases. Other cases of serious LSA intoxication are published, including a death. It is important to inform about the risks related to LSA consumption, a substance which is freely available and sometimes hidden behind various plant names.

Pre-hospital identification and post-recovery challenges of intoxication with synthetic cannabinoid containing legal high products such as 'Exodus Damnation'.

This short report describes the case of a young adult male who had smoked a synthetic cannabinoid legal high product called 'Exodus Damnation'. The patient's presentation was atypical from that described in the literature, with hypotension and hypoxaemia. Of note was the rapid recovery after pre-hospital intervention with high-flow oxygen therapy and intravenous fluids. The patient refused on-going care, despite repeated advice to attend the Emergency Department. The distinct lack of specialist support and referral to drug treatment for this patient population, with whom ambulance services are coming into contact with increasing frequency, is reported. For those patients with the capacity to refuse on-going care, ambulance services may be in an opportune position to actively promote referral to support services for these vulnerable individuals.

Deaths of individuals aged 16-24 years in the UK after using mephedrone.

OBJECTIVE: Mephedrone is a stimulant drug chemically related to amphetamine, with effects similar to those of amphetamine and cocaine. This study aims to analyse fatalities following ingestion of mephedrone in the UK amongst 16- to 24-year-olds in 2009-2013, providing an update on data presented at the 2nd International Conference on Novel Psychoactive Substances. METHODS: A literature search was undertaken to identify published information on pharmacology, toxicity and fatalities associated with mephedrone. Fatalities involving mephedrone were extracted from the National Programme on Substance Abuse Deaths database, which receives information on drug-related deaths from coroners in the UK and Islands and other data suppliers. Selection criteria are as follows: deceased aged 16-24 years at time of death and mephedrone directly implicated in the cause of death and/or mentioned in the coroner's verdict. RESULTS: Thirty cases met the study criteria, and when known, all were of White ethnicity, most (85%) had a history of drug use and 73% were male. Two-thirds (63%) were accidental poisonings. Mephedrone was used with other substances in most cases (87%); other substances were implicated in 60% of deaths. CONCLUSIONS: Mephedrone use can have potentially fatal consequences, especially in combination with other substances. Deaths from its use in the 16-24 years' age group continue to occur in the UK, despite it being a controlled drug. Health professionals and potential consumers should be alert to this risk.

Methoxetamine-related deaths in the UK: an overview.

OBJECTIVE: The goal of this study is to provide an update on the data given on methoxetamine (MXE)-related fatalities that occurred in 2011-2013, presented at the Second International Conference on Novel Psychoactive Substances. METHODS: Fatalities involving MXE were extracted from the database of the National Programme on Substance Abuse Deaths, which receives information on drug-related deaths from Coroners in the UK and Islands (Isle of Man, Jersey, Guernsey) and other data suppliers. RESULTS: Eight cases, received by 3 September 2013, in which MXE was found at post-mortem and/or directly implicated in the death and/or mentioned in the Coroner's verdict are described. The median age at death was 27 years, with the majority of White ethnicity (6/8) and male (7/8). MXE was used together with other substances in 7/8 cases. MXE was found at post-mortem in all cases, directly implicated in the deaths of four and likely to have had an influence in two. CONCLUSIONS: More research needs to be conducted into its health effects and toxicity potential. Health care professionals should be made aware of the potential health harms of MXE, in order to develop early intervention measures and minimise the number of MXE-related poisonings and fatalities.

Development of gas chromatography-mass spectrometry (GC-MS) and other rapid screening methods for the analysis of 16 'legal high' cathinone derivatives.

The prevalence of so-called 'legal high' drugs in forensic science drug casework has increased markedly in recent years. This has given rise to both legal and analytical challenges in the identification of these substances. The requirement for validated, reliable and rapid testing methodologies for these compounds is obvious. This work reports the analysis of sixteen synthesised cathinone derivatives encountered in casework using presumptive testing, thin layer chromatography and gas chromatography-mass spectrometry (GC-MS).

Identification of 5F-Cumyl-PINACA, a Synthetic Cannabinoid, in the Herbal Material Used for Recreational Purposes in the Province of Trieste: Public Health Implications.

BACKGROUND: In recent years, the phenomenon of the production and trade of synthetic cannabinoids has grown, becoming a public health issue worldwide. The recent access- to the ED of the hospital of Trieste- of people who complained of episodes of hallucinations, sensation of poisoning, tachycardia, and air hunger following the inhalation of "Che Sballo platinum", have highlighted the need to perform further analysis on the contents of the packet sold as an air freshener, produced in Koper (Slovenia). OBJECTIVE: This paper wants to be an alert about the possible consequences on health due to the spreading of "Che Sballo platinum" in the province of Trieste. METHODS: The package contents were analyzed by a multi-target screening method of MRM-IDAEPI experiment. The result was then confirmed, and quantification was achieved via LC-ESI-MS/MS analysis in MRM mode using QTrap 6500 + Sinergy hydro column 100 x 2 mm 1.9 um transitions MRM1 368.3 → 250.0; MRM2 368.3 → 233.0. RESULTS: The initial screening tested negative for THC and showed positive results for 5F-Cumyl- PINACA. Quantitation result reported dose by the package of 8.5 mg of the compound. Formal notification was sent to the Italian Health Authorities (Notification No. 2021110205). CONCLUSION: Consumption of 5F-Cumyl-PINACA results in much more potent effects than marijuana. Lack of information about the actual concentration of the substance on the packaging does not allow drug users to have an adequate dosage, with possible toxic consequences on health. Further investigations must be done to discover the true extent of the phenomenon.

Dokha brand differentiation by elemental analysis measured by inductively coupled plasma-mass spectrometry.

Dokha is a tobacco product commonly used in Middle Eastern and Northern African regions. It is available in three blends purportedly corresponding to the degree of "buzz" experienced by the user. The "buzz" has been linked in part to nicotine levels, which are higher than those found in cigarettes and is believed to be the reason dokha is abused as a "legal high." There have been reports of seizure activity from dokha users, and elevated concentrations of toxic metals have been measured in dokha tobacco. The purpose of this work was to determine whether we could use dokha's elemental content, measured by inductively coupled plasma-mass spectrometry, to link dokha back to its brand. This could aid investigators in identifying brands and/or distribution routes in the case of adverse effects resulting from dokha use. We measured the concentrations of Mg, K, Mn, Ni, Cu, Rb, Sr, and Ba in Medwakh, Nirvana, Scorpion, Enjoy, Kingdom, and Iconic dokha brands. Analysis of variance revealed statistical differences in concentrations of elements among groups. Discriminant function analysis (using leave-one-out classification) was 58.3% successful at differentiating brands. Enjoy dokha was the most, and Kingdom dokha the least, correctly classified among groups. Attempts to further link dokha blends back to light, medium, and heavy blends were less successful. These results indicate potential for using elemental content to discriminate among dokha brands. Our data may also help to understand the degree of additional processing and/or adulteration of dokha products available to users in the United States.

Pharmacological characterizations of the 'legal high' fluorolintane and isomers.

1,2-Diarylethylamines represent a class of molecules that have shown potential in the treatment of pain, epilepsy, neurodegenerative disease and depression. Examples include lefetamine, remacemide, and lanicemine. Recently, several 1,2-diarylethylamines including the dissociatives diphenidine, methoxphenidine and ephenidine as well as the opioid MT-45, have appeared as 'research chemicals' or 'legal highs'. Due to their recent emergence little is known about their pharmacology. One of these, 1-[1-(2-fluorophenyl)-2-phenylethyl]pyrrolidine (fluorolintane, 2-F-DPPy), is available for purchase with purported dissociative effects intended to resemble phencyclidine (PCP) and ketamine. To better understand this emerging class, pharmacological investigations were undertaken for the first time on fluorolintane and its five aryl-fluorine-substituted isomers. In vitro binding studies revealed high affinity for N-methyl-D-aspartate (NMDA) receptors with fluorolintane (Ki = 87.92 nM) with lesser affinities for related compounds. Additional affinities were seen for all compounds at several sites including norepinephrine (NET), serotonin (SERT) and dopamine (DAT) transporters, and sigma receptors. Notably high affinities at DAT were observed, which were in most cases greater than NMDA receptor affinities. Additional functional and behavioral experiments show fluorolintane inhibited NMDA receptor-induced field excitatory postsynaptic potentials in rat hippocampal slices and inhibited long-term potentiation induced by theta-burst stimulation in rat hippocampal slices with potencies consistent with its NMDA receptor antagonism. Finally fluorolintane inhibited prepulse inhibition in rats, a measure of sensorimotor gating, with a median effective dose (ED50) of 13.3 mg/kg. These findings are consistent with anecdotal reports of dissociative effects of fluorolintane in humans.

Development of a PCR High-Resolution Melt Assay for Artemisia absinthium (Wormwood) and a Triplex Assay with Two Additional "Unregulated Legal High" Species Datura stramonium (Jimson Weed) and Merremia tuberosa (Hawaiian Woodrose).

Artemisia absinthium (wormwood), a common ingredient in absinthe, contains the compound thujone, which is unregulated by the U.S. Drug Enforcement Agency. Thujone can cause an "unregulated legal high" in higher concentrations. The European Union limits thujone from Artemisia species to 35 mg/kg while the U.S. Food and Drug Administration requires less than 10 ppm to be "thujone-free." However, individuals can smoke or ingest A. absinthium in different forms. This study developed a polymerase chain reaction (PCR) high-resolution melt (HRM) assay to detect and identify A. absinthium based on primer specificity, sensitivity, repeatability, and robustness. A triplex assay was performed with three "unregulated legal high" species: Datura stramonium, Merremia tuberosa, and A. absinthium; the PCR HRM assay detected and identified each plant at melt temperatures 77.42 ± 0.20°C, 83.88 ± 0.22°C, and 87.77 ± 0.15°C, respectively. The primer set developed distinguished A. absinthium from a variety of plant species and was successfully triplexed.

Fluorinated phenmetrazine "legal highs" act as substrates for high-affinity monoamine transporters of the SLC6 family.

A variety of new psychoactive substances (NPS) are appearing in recreational drug markets worldwide. NPS are compounds that target various receptors and transporters in the central nervous system to achieve their psychoactive effects. Chemical modifications of existing drugs can generate NPS that are not controlled by current legislation, thereby providing legal alternatives to controlled substances such as cocaine or amphetamine. Recently, 3-fluorophenmetrazine (3-FPM), a derivative of the anorectic compound phenmetrazine, appeared on the recreational drug market and adverse clinical effects have been reported. Phenmetrazine is known to elevate extracellular monoamine concentrations by an amphetamine-like mechanism. Here we tested 3-FPM and its positional isomers, 2-FPM and 4-FPM, for their abilities to interact with plasma membrane monoamine transporters for dopamine (DAT), norepinephrine (NET) and serotonin (SERT). We found that 2-, 3- and 4-FPM inhibit uptake mediated by DAT and NET in HEK293 cells with potencies comparable to cocaine (IC50 values < 2.5 µM), but display less potent effects at SERT (IC50 values >80 µM). Experiments directed at identifying transporter-mediated reverse transport revealed that FPM isomers induce efflux via DAT, NET and SERT in HEK293 cells, and this effect is augmented by the Na+/H+ ionophore monensin. Each FPM evoked concentration-dependent release of monoamines from rat brain synaptosomes. Hence, this study reports for the first time the mode of action for 2-, 3- and 4-FPM and identifies these NPS as monoamine releasers with marked potency at catecholamine transporters implicated in abuse and addiction. This article is part of the Special Issue entitled 'Designer Drugs and Legal Highs.'

Neurotoxicity screening of new psychoactive substances (NPS): Effects on neuronal activity in rat cortical cultures using microelectrode arrays (MEA).

While the prevalence and the use of new psychoactive substances (NPS) is steadily increasing, data on pharmacological, toxicological and clinical effects is limited. Considering the large number of NPS available, there is a clear need for efficient in vitro screening techniques that capture multiple mechanisms of action. Neuronal cultures grown on multi-well microelectrode arrays (mwMEAs) have previously proven suitable for neurotoxicity screening of chemicals, pharmaceuticals and (illicit) drugs. We therefore used rat primary cortical cultures grown on mwMEA plates to investigate the effects of eight NPS (PMMA, α-PVP, methylone, MDPV, 2C-B, 25B-NBOMe, BZP and TFMPP) and two 'classic' illicit drugs (cocaine, methamphetamine) on spontaneous neuronal activity. All tested drugs rapidly and concentration-dependently decreased the weighted mean firing rate (wMFR) and the weighted mean burst rate (wMBR) during a 30 min acute exposure. Of the 'classic' drugs, cocaine most potently inhibited the wMFR (IC50 9.8 µM), whereas methamphetamine and the structurally-related NPS PMMA were much less potent (IC50 100 µM and IC50 112 µM, respectively). Of the cathinones, MDPV and α-PVP showed comparable IC50 values (29 µM and 21 µM, respectively), although methylone was 10-fold less potent (IC50 235 µM). Comparable 10-fold differences in potency were also observed between the hallucinogenic phenethylamines 2C-B (IC50 27 µM) and 25B-NBOMe (IC50 2.4 µM), and between the piperazine derivatives BZP (IC50 161 µM) and TFMPP (IC50 19 µM). All drugs also inhibited the wMBR and concentration-response curves for wMBR and wMFR were comparable. For most drugs, IC50 values are close to the estimated human brain concentrations following recreational doses of these drugs, highlighting the importance of this efficient in vitro screening approach for classification and prioritization of emerging NPS. Moreover, the wide range of IC50 values observed for these and previously tested drugs of abuse, both within and between different classes of NPS, indicates that additional investigation of structure-activity relationships could aid future risk assessment of emerging NPS.

Psychotic due to bath salts and methamphetamines: emergency cesarean section under general anesthesia.

The use of "bath salts" or other new psychoactive substances, otherwise known as "legal highs", is increasing. Illicit drug use during pregnancy is not uncommon. Nevertheless, literature reporting bath salts and their effect on pregnancy is scant. Besides, there seems to be no literature about bath salts and conduct of general anesthesia. This case report describes a general anesthetic for the surgical delivery of an infant to a woman under the acute influence of bath salts and methamphetamines.

Identification of new psychoactive substances (NPS) using handheld Raman spectroscopy employing both 785 and 1064nm laser sources.

The chemical identification of new psychoactive substances (NPS) in the field is challenging due not only to the plethora of substances available, but also as a result of the chemical complexity of products and the chemical similarity of NPS analogues. In this study, handheld Raman spectroscopy and the use of two excitation wavelengths, 785 and 1064nm, were evaluated for the identification of 60 NPS products. The products contained a range of NPS from classes including the aminoindanes, arylalkylamines, benzodiazepines, and piperidines & pyrrolidines. Identification was initially assessed using the instruments' in built algorithm (i.e., % HQI) and then further by visual inspection of the Raman spectra. Confirmatory analysis was preformed using gas chromatography mass spectrometry. For the 60 diverse products, an NPS was successfully identified via the algorithm in 11 products (18%) using the 785nm source and 29 products (48%) using the 1064nm source. Evaluation of the Raman spectra showed that increasing the excitation wavelength from 785 to 1064nm improved this 'first pass' identification primarily due to a significant reduction in fluorescence, which increased S/N of the characteristic peaks of the substance identified. True positive correlations between internet products and NPS signatures ranged from 57.0 to 91.3% HQI with typical RSDs<10%. Tablet formulations and branded products were particularly challenging as a result of low NPS concentration and high chemical complexity, respectively. This study demonstrates the advantage of using a 1064nm source with handheld Raman spectroscopy for improved 'first pass' NPS identification when minimal spectral processing is required, such as when working in field. Future investigations will focus on the use of mixture algorithms, effect of NPS concentration, and further improvement of spectral libraries.

Mitragynine concentrations in two fatalities.

Two cases of fatalities are reported of which the recreational use of Mitragyna speciosa ("kratom") could be confirmed. One of these cases presents with one of the highest postmortem mitragynine concentrations published to date. Our results show that even extremely high mitragynine blood concentrations following the consumption of kratom do not necessarily have to be the direct cause of death in such fatalities as a result of an acute overdose. The two cases are compared with regard to the differences in mitragynine concentrations detected and the role of mitragynine in the death of the subjects. Irrespective of the big differences in mitragynine concentrations in the postmortem blood samples, mitragynine was not the primary cause of death in either of the two cases reported here. Additionally, by rough estimation, a significant difference in ratio of mitragynine to its diastereomers in the blood and urine samples between the two cases could be seen.

Psychiatric symptoms and synthetic cannabinoid use: Information for clinicians.

BACKGROUND: Limited treatment information is available when patients present with psychotic symptoms secondary to synthetic cannabinoid (SC) use. Symptoms associated with use are often indistinguishable from those encountered with a primary mental illness and also include aggression, confusion, and anxiety. For these patients, clinicians rely on physical presentation, symptom(s) onset, and episode duration when evaluating patients. PATIENT HISTORY: An adult man was involuntarily admitted to inpatient status secondary to reports of bizarre behaviors that included paranoia and psychomotor agitation. Because of the severity of the symptoms, he was unable to participate in the admission assessment. On day 2, he reported having smoked a substance provided by a friend. In addition, he admitted to previous SC use on 3 occasions, with each occasion resulting in an involuntary admission to inpatient status. The course of this admission was unremarkable. CONCLUSIONS: A brief overview of psychiatric signs and symptoms of SC use and information to help clinicians are included. The presentation of psychotic symptoms secondary to SC may be consistent with those of psychosis or other substances of abuse. Because of the variability in the symptoms produced by SC use, clinicians are encouraged to consider SC use in the diagnostic evaluation.

Ephenidine: A new psychoactive agent with ketamine-like NMDA receptor antagonist properties.

To avoid legislation based on chemical structure, research chemicals, frequently used for recreational purposes, are continually being synthesized. N-Ethyl-1,2-diphenylethanamine (ephenidine) is a diarylethylamine that has recently become popular with recreational users searching for dissociative hallucinogenic effects. In the present study, the pharmacological basis of its neural actions has been investigated, initially by assessing its profile in central nervous system receptor binding assays and subsequently in targeted electrophysiological studies. Ephenidine was a potent inhibitor of 3H-MK-801 binding (Ki: 66 nM), implying that it acts at the PCP site of the N-methyl-d-aspartate (NMDA) receptor. It also showed modest activity at dopamine (379 nM) and noradrenaline (841 nM) transporters and at sigma 1 (629 nM) and sigma 2 (722 nM) binding sites. In experiments of extracellular recording of field excitatory postsynaptic potentials (fEPSPs) from area CA1 of rat hippocampal slices, ephenidine, 1 and 10 µM, respectively, produced a 25% and a near maximal inhibition of the NMDA receptor mediated fEPSP after 4 h superfusion. By contrast, ephenidine (50 µM) did not affect the AMPA receptor mediated fEPSPs. In whole cell patch clamp recordings, from hippocampal pyramidal cells, ephenidine (10 µM) blocked NMDA receptor-mediated EPSCs in a highly voltage-dependent manner. Additionally, ephenidine, 10 µM, blocked the induction of long term potentiation (LTP) in CA1 induced by theta burst stimulation. The present data show that the new psychoactive substance, ephenidine, is a selective NMDA receptor antagonist with a voltage-dependent profile similar to ketamine. Such properties help explain the dissociative, cognitive and hallucinogenic effects in man. This article is part of the Special Issue entitled 'Ionotropic glutamate receptors'.

No Laughing Matter: Presence, Consumption Trends, Drug Awareness, and Perceptions of "Hippy Crack" (Nitrous Oxide) among Young Adults in England.

In clinical settings, nitrous oxide gas is a safe anesthetic used during childbirth, in dentistry, and to relieve anxiety in emergencies. Colloquially known as "hippy crack"' or "laughing gas," it is increasingly taken recreationally for its euphoric and relaxing effects and hallucinogenic properties. Using a self-reported survey, we gathered quantitative and qualitative information on users and non-users of hippy crack among a young population regarding: consumption patterns, knowledge, risk awareness and intentions toward future abuse. Quantitative responses from a total of 140 participants were analyzed for frequencies and relationships, whereas qualitative data were evaluated via identifying the reoccurring themes. Overall, 77.1% (n = 108) had heard of hippy crack and 27.9% (n = 39) admitted to past-year use. Prior users mostly indicated intended future use, had an average low number of past-year uses but some with > 20 occasions, had a varied number of inhalations per occasion (often 1-10) with an effect lasting up to 5 min, and a majority preferred social rather than lone use. For non-users, 79.2% said they would take hippy crack with the vast majority (94%) preferring a social setting. The results show a concerning gap between available evidence and awareness of side effects. Despite serious reported side effects, including psychosis and myeloneuropathy-especially on the young developing brain-only a minority (29.3%) was aware of any side effects. In contrast, in a hypothetical scenario depicting a first social encounter with hippy crack, the qualitative responses were in contrast to qualitative outcomes revealing that participants would try (n = 30)/not try (n = 25) it, would feel under pressure to try it (n = 6) with only 11 opting to exit the situation. In summary, this first report of trends and perceptions of the use of hippy crack among young adults in the England highlights a lack of concern with side effects, coupled to a willingness to partake. Because typical users are young with risks to the still developing brain, education about the nitrous oxide abuse is warranted to prevent impaired brain development. Further studies to investigate the possible effects of nitrous oxide on the developing brain in young adults would advance meaningful prevention.