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Neuroscience Feb 2023Psychostimulant drugs, such as cocaine, d-amphetamine and methylphenidate, alter a wide range of behaviors including locomotor activity and somatosensory perception....
Psychostimulant drugs, such as cocaine, d-amphetamine and methylphenidate, alter a wide range of behaviors including locomotor activity and somatosensory perception. These altered behaviors are accompanied by the activation of specific neuronal populations within reward-, emotion- and locomotion-related circuits. However, whether such regulation occurs at the level of the spinal cord, a key node for neural circuits integrating and coordinating sensory and motor functions has never been addressed. By evaluating the temporal and spatial expression pattern of the phosphorylated form of the immediate early gene cFos at Ser32 (pS32-cFos), used as a proxy of neuronal activation, we demonstrate that, in adult male mice, d-amphetamine increases pS32-cFos expression in both inhibitory and excitatory neurons in dorsal and ventral horns at the lumbar spinal cord level. Interestingly, a fraction of neurons activated by a first exposure to d-amphetamine can be re-activated following d-amphetamine re-exposure. Similar expression patterns were observed in response to cocaine and methylphenidate, but not following morphine and dozilcipine administration. Finally, the blockade of dopamine reuptake was sufficient to recapitulate the increase in pS32-cFos expression induced by psychostimulant drugs. Our work provides evidence that cFos expression can be activated in lumbar spinal cord in response to acute psychostimulants administration.
Topics: Male; Mice; Animals; Amphetamine; Pharmaceutical Preparations; Central Nervous System Stimulants; Cocaine; Methylphenidate; Spinal Cord; Dextroamphetamine
PubMed: 36502959
DOI: 10.1016/j.neuroscience.2022.12.005 -
Cells Jan 2022Exposure to methamphetamine (Meth) has been classically associated with damage to neuronal terminals. However, it is now becoming clear that addiction may also result...
Exposure to methamphetamine (Meth) has been classically associated with damage to neuronal terminals. However, it is now becoming clear that addiction may also result from the interplay between glial cells and neurons. Recently, we demonstrated that binge Meth administration promotes microgliosis and microglia pro-inflammation via astrocytic glutamate release in a TNF/IPR2-Ca-dependent manner. Here, we investigated the contribution of neuronal cells to this process. As the crosstalk between microglia and neurons may occur by contact-dependent and/or contact-independent mechanisms, we developed co-cultures of primary neurons and microglia in microfluidic devices to investigate how their interaction affects Meth-induced microglia activation. Our results show that neurons exposed to Meth do not activate microglia in a cell-autonomous way but require astrocyte mediation. Importantly, we found that neurons can partially prevent Meth-induced microglia activation via astrocytes, which seems to be achieved by increasing arginase 1 expression and strengthening the CD200/CD200r pathway. We also observed an increase in synaptic individual area, as determined by co-localization of pre- and post-synaptic markers. The present study provides evidence that contact-dependent mechanisms between neurons and microglia can attenuate pro-inflammatory events such as Meth-induced microglia activation.
Topics: Methamphetamine; Microglia; Neuroglia; Neuronal Plasticity; Neurons
PubMed: 35159165
DOI: 10.3390/cells11030355 -
The Journal of Pharmacology and... Aug 2021Monoamine releasers such as d-methamphetamine (d-MA) can reduce cocaine use in laboratory studies and have been forwarded for the management of cocaine use disorder...
Monoamine releasers such as d-methamphetamine (d-MA) can reduce cocaine use in laboratory studies and have been forwarded for the management of cocaine use disorder (CUD). However, the proven abuse liability of d-MA has limited enthusiasm for clinical use. The levorotatory isomer of MA, l-MA, appears to have lesser stimulant effects, possibly due to its preferential norepinephrine-releasing properties compared with dopamine. The present study evaluated the abuse potential of l-MA by comparing its reinforcing effects with known stimulant drugs of abuse in nonhuman primates. Adult rhesus macaques ( = 4) responded for intravenous injections of cocaine, d-MA, methcathinone (MCAT), or l-MA under a fixed-ratio (FR) schedule of reinforcement; reinforcing effectiveness was evaluated using behavioral economic demand procedures. In a separate cohort ( = 9), daily activity and food-reinforced responding were assessed during 100 days of treatment with daily dosages of l-MA (2.3 mg/kg per day, i.v.) or d-MA (0.74 mg/kg per day, i.v.) previously shown to decrease cocaine self-administration. Results show that all drugs maintained self-administration, with peak injections reaching ∼100 inj per session for cocaine, MCAT, and d-MA and ∼50 inj per session for l-MA . In demand studies, self-administration of each drug gradually decreased as FR size increased. The exponential model of demand indicated that the reinforcing effectiveness of l-MA was significantly less than the other drugs studied. Chronic l-MA treatment did not appreciably alter daily activity and only transiently suppressed food-reinforced responding. These data, coupled with previous findings that l-MA effectively reduces stimulant self-administration, suggest that l-MA, or other norepinephrine-preferring releasers, may serve as agonist medication for CUD with lesser abuse liability than common psychostimulants. SIGNIFICANCE STATEMENT: Development of pharmacotherapies for cocaine use disorder remains a formidable challenge. Agonist-based therapies show promise, but enthusiasm is tempered by the abuse liability of previously proposed medications. This study evaluated the abuse liability and chronic treatment effects of methamphetamine's levorotatory isomer (l-MA). l-MA demonstrated lower abuse liability compared with commonly abused stimulants and produced few untoward effects. In the context of recent studies demonstrating that l-MA attenuates stimulant self-administration, these findings support l-MA's potential as a pharmacotherapy for stimulant addiction.
Topics: Central Nervous System Stimulants; Methamphetamine; Reinforcement, Psychology
PubMed: 33986037
DOI: 10.1124/jpet.121.000548 -
PloS One 2023Ephedra sinica Stapf. is a shrubby plant widely used in traditional Chinese medicine due to its high level of medicinal value, thus, it is in high demand. Ephedrine (E)...
Ephedra sinica Stapf. is a shrubby plant widely used in traditional Chinese medicine due to its high level of medicinal value, thus, it is in high demand. Ephedrine (E) and pseudoephedrine (PE) are key medicinal components and quality indicators for E. sinica. These two ephedrine-type alkaloids are basic elements that exert the medicinal effect of E. sinica. Recently, indiscriminate destruction and grassland desertification have caused the quantity and quality of these pharmacological plants to degenerate. Predicting potentially suitable habitat for high-quality E. sinica is essential for its future conservation and domestication. In this study, MaxEnt software was utilized to map suitable habitats for E. sinica in Inner Mongolia based on occurrence data and a set of variables related to climate, soil, topography and human impact. The model parametrization was optimized by evaluating alternative combinations of feature classes and values of the regularization multiplier. Second, a geospatial quality model was fitted to relate E and PE contents to the same environmental variables and to predict their spatial patterns across the study area. Outputs from the two models were finally coupled to map areas predicted to have both suitable conditions for E. sinica and high alkaloid content. Our results indicate that E. sinica with high-quality E content was mainly distributed in the Horqin, Ulan Butong and Wulanchabu grasslands. E. sinica with high-quality PE content was primarily found in the Ordos, Wulanchabu and Ulan Butong grasslands. This study provides scientific information for the protection and sustainable utilization of E. sinica. It can also help to control and prevent desertification in Inner Mongolia.
Topics: Humans; Ephedrine; Ephedra sinica; Alkaloids; Drugs, Chinese Herbal; China; Pseudoephedrine; Ephedra
PubMed: 37083689
DOI: 10.1371/journal.pone.0283967 -
Journal of Psychopharmacology (Oxford,... Mar 2022Mescaline is a naturally occurring psychoactive phenethylamine found in several cacti and historically used ceremonially by Indigenous and Latin American populations....
BACKGROUND
Mescaline is a naturally occurring psychoactive phenethylamine found in several cacti and historically used ceremonially by Indigenous and Latin American populations. Broader recognition of its possible therapeutic value in Western science began in the 1950s; however, knowledge of the safety profile of mescaline and the extent of its use remains limited. The primary aim of this study is to examine the epidemiology of mescaline use among English-speaking adults.
METHODS
About 452 respondents completed a web-based survey designed to assess their previous experience with mescaline (subjective effects, outcome measures, and mescaline type used).
RESULTS
Most respondents reported that they had consumed mescaline infrequently (⩽once/year), for spiritual exploration or to connect with nature (74%). A small number of respondents reported drug craving/desire (9%), whereas very few reported legal (1%), or psychological problems (1%) related to its use, and none reported seeking any medical attention. Overall, respondents rated the acute mystical-type effects as "," ego-dissolution and psychological insight effects as "," and challenging effects as "." Most respondents reported that they used Peyote and San Pedro in their most memorable mescaline experience. Overall, the intensity of acute mescaline effects did not differ between mescaline types. About 50% of the sample reported having a psychiatric condition (i.e. depression, anxiety, etc.), and most (>67%) reported improvements in these conditions following their most memorable experience with mescaline.
CONCLUSION
Findings indicate that the mescaline in any form may produce a psychedelic experience that is associated with the spiritual significance and improvements in the mental health with low potential for abuse.
Topics: Adult; Hallucinogens; Humans; Mental Disorders; Mescaline; Motivation; Surveys and Questionnaires
PubMed: 33949246
DOI: 10.1177/02698811211013583 -
Substance Use & Misuse 2023: Drug-related deaths in the US continue to increase. Sentinel surveillance of high-risk populations can provide early warning for shifts in trends. Nightclub/festival...
Exploring Potential Bellwethers for Drug-Related Mortality in the General Population: A Case for Sentinel Surveillance of Trends in Drug Use among Nightclub/Festival Attendees.
: Drug-related deaths in the US continue to increase. Sentinel surveillance of high-risk populations can provide early warning for shifts in trends. Nightclub/festival attendees have high levels of drug use, so we explored whether use among this population can serve as a potential bellwether or indicator for use-related mortality in the general population.: Trends in past-year cocaine and methamphetamine use were estimated from nightclub/festival attendees in New York City (NYC) and among NY residents, and trends were estimated for related death rates in NYC (2014/15-2019/20). Using national data from England and Wales (2010-2019), trends in past-year cocaine and ecstasy use (among the full population and among nightclub attendees) and related deaths were also estimated.: In NY/NYC, cocaine use remained stable in the general population, but use among nightclub/festival attendees and cocaine-related deaths doubled. Methamphetamine use among nightclub/festival attendees and death rates also more than doubled while use among the general population remained stable. In UK countries, increases in cocaine and ecstasy use were larger for infrequent/frequent nightclub attendees than in the general population, with 3.6- and 8-fold increases in related deaths, respectively. In UK countries, the association between nightclub attendance and death rates increased in a dose-response-like manner with larger associations detected when death rates were lagged by one year.: Patterns of use among nightclub/festival attendees, more so than patterns in the general population, were similar to patterns of drug-related deaths. Use among this subpopulation could possibly serve as a bellwether for use-related outcomes. Continued surveillance is recommended.
Topics: Humans; Illicit Drugs; Holidays; Sentinel Surveillance; Substance-Related Disorders; N-Methyl-3,4-methylenedioxyamphetamine; Methamphetamine; Cocaine
PubMed: 36469638
DOI: 10.1080/10826084.2022.2151315 -
The Science of the Total Environment Jan 2023The outbreak and spread of COVID-19 impacted through various ways the lives of millions of humans globally. In this work, wastewater-based epidemiology (WBE) was applied...
The outbreak and spread of COVID-19 impacted through various ways the lives of millions of humans globally. In this work, wastewater-based epidemiology (WBE) was applied to investigate the effect of the actions taken by the Republic of Cyprus to confine COVID-19 on the use of illicit stimulant drugs. Daily influent samples were collected from the six main wastewater treatment plants (WWTPs) of the country i) before lockdown (3-9 April 2019), ii) during lockdown (21-27 April 2020), iii) during the post-lockdown period (14-20 July 2020), and, iv) during each season of the following year (20-26 April 2021, 19-25 July 2021, 11-17 October 2021, 25 December 2021-2 January 2022), and analyzed for amphetamine, methamphetamine, MDMA and cocaine. In most areas, amphetamine and methamphetamine use was not affected during the confinement period, but as availability of the substances decreased with time, a drop in their use was observed when most restriction measures were eased (up to 9- and 22-fold decrease, respectively). The limitations on social interactions and events during the quarantine period seem to have led to the reduction of MDMA and cocaine and driven a sharp decrease of their use in most areas studied (up to 11 and 6 times lower, respectively). However, the re-opening of activities led to a pronounced consumption increase, reaching maximum daily values of 800 and 2691 mg/1000 inhabitants/day, respectively. In 2021, drug use was re-established to lower levels. The examination of weekly patterns during this year revealed higher weekend use of methamphetamine, MDMA and cocaine. Our results suggest that both the implementation and the easing of COVID-19 related measures affected the availability and the use of drugs. This study also provides the first insight on the consumption of illicit drugs in the Republic of Cyprus during pre-, post- and pandemic times and demonstrates the importance of WBE.
Topics: Humans; Illicit Drugs; Wastewater; Pandemics; N-Methyl-3,4-methylenedioxyamphetamine; Cyprus; Chromatography, Liquid; Tandem Mass Spectrometry; Substance Abuse Detection; Water Pollutants, Chemical; COVID-19; Communicable Disease Control; Substance-Related Disorders; Methamphetamine; Amphetamine; Cocaine
PubMed: 36108831
DOI: 10.1016/j.scitotenv.2022.158747 -
Addiction (Abingdon, England) Jan 2020Wastewater-based epidemiology is an additional indicator of drug use that is gaining reliability to complement the current established panel of indicators. The aims of...
BACKGROUND AND AIMS
Wastewater-based epidemiology is an additional indicator of drug use that is gaining reliability to complement the current established panel of indicators. The aims of this study were to: (i) assess spatial and temporal trends of population-normalized mass loads of benzoylecgonine, amphetamine, methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) in raw wastewater over 7 years (2011-17); (ii) address overall drug use by estimating the average number of combined doses consumed per day in each city; and (iii) compare these with existing prevalence and seizure data.
DESIGN
Analysis of daily raw wastewater composite samples collected over 1 week per year from 2011 to 2017.
SETTING AND PARTICIPANTS
Catchment areas of 143 wastewater treatment plants in 120 cities in 37 countries.
MEASUREMENTS
Parent substances (amphetamine, methamphetamine and MDMA) and the metabolites of cocaine (benzoylecgonine) and of Δ -tetrahydrocannabinol (11-nor-9-carboxy-Δ -tetrahydrocannabinol) were measured in wastewater using liquid chromatography-tandem mass spectrometry. Daily mass loads (mg/day) were normalized to catchment population (mg/1000 people/day) and converted to the number of combined doses consumed per day. Spatial differences were assessed world-wide, and temporal trends were discerned at European level by comparing 2011-13 drug loads versus 2014-17 loads.
FINDINGS
Benzoylecgonine was the stimulant metabolite detected at higher loads in southern and western Europe, and amphetamine, MDMA and methamphetamine in East and North-Central Europe. In other continents, methamphetamine showed the highest levels in the United States and Australia and benzoylecgonine in South America. During the reporting period, benzoylecgonine loads increased in general across Europe, amphetamine and methamphetamine levels fluctuated and MDMA underwent an intermittent upsurge.
CONCLUSIONS
The analysis of wastewater to quantify drug loads provides near real-time drug use estimates that globally correspond to prevalence and seizure data.
Topics: Amphetamine; Chromatography, Liquid; Cocaine; Environmental Monitoring; Humans; Illicit Drugs; Internationality; Methamphetamine; N-Methyl-3,4-methylenedioxyamphetamine; Spatio-Temporal Analysis; Substance Abuse Detection; Tandem Mass Spectrometry; Wastewater
PubMed: 31642141
DOI: 10.1111/add.14767 -
Molecules (Basel, Switzerland) Oct 2021The analysis of psychoactive substances in hair is of great importance for both clinical and forensic toxicologists since it allows one to evaluate past and continuative...
The analysis of psychoactive substances in hair is of great importance for both clinical and forensic toxicologists since it allows one to evaluate past and continuative exposure to xenobiotics. In particular, a new challenge is represented by new psychoactive substances: Among this new class of drugs of abuse, synthetic cathinone and phenethylamine derivatives are often detected in biological samples. Hence, there is a growing need to develop new analytical procedures or improve old ones in order to conduct evaluations of these emerging substances. This study is a systematic review of all the instrumental and experimental data available in the literature. A total of 32 articles were included in the review. Acidic solvents proved to be the most reliable solutions for extraction. Gas chromatography and liquid chromatography coupled to tandem mass spectrometric and high-resolution mass spectrometric systems represent the majority of the involved instrumental techniques. Sensitivity must be maintained at the pg/mg level to detect any occurrences up to occasional consumption. In total, 23 out of 32 articles reported real positive samples. The most frequently detected substance in hair was mephedrone, followed by butylone, methylone, MDPV, and α-pyrrolidinophenone-type substances.
Topics: Alkaloids; Chromatography, Liquid; Forensic Toxicology; Gas Chromatography-Mass Spectrometry; Hair; Humans; Illicit Drugs; Limit of Detection; Phenethylamines; Substance Abuse Detection; Tandem Mass Spectrometry
PubMed: 34684725
DOI: 10.3390/molecules26206143 -
Current Neuropharmacology 2020To systematically review the literature on the therapeutic use of amphetamine, lisdexamfetamine and methylphenidate in elderly population with and without dementia.
OBJECTIVE
To systematically review the literature on the therapeutic use of amphetamine, lisdexamfetamine and methylphenidate in elderly population with and without dementia.
METHODS
We conducted two researches on the PubMed, Scopus and Embase using the keywords ("elderly") AND ("amphetamine" OR "methylphenidate" OR "lisdexamfetamine") and then ("Alzheimer" OR "dementia") AND ("amphetamine" OR "methylphenidate" OR "lisdexamfetamine").
RESULTS
Twenty-nine papers met all the eligibility criteria. The results are encouraging as 81.5% of the studies showed clinical improvement of the investigated condition.
CONCLUSION
Amphetamines and methylphenidate are probably effective strategies for different conditions in the elderly population. However, further studies are needed to provide more robust evidence on efficacy, dosage and safety for this population.
Topics: Aged; Amphetamine; Dementia; Depressive Disorder, Major; Humans; Lisdexamfetamine Dimesylate; Methylphenidate
PubMed: 31660835
DOI: 10.2174/1570159X17666191010093021