Addiction
July 21, 2011
Celia J. A. Morgan, H. Valerie Curran
645 citations
Repeated misuse of ketamine, both acute and chronic, causes significant physical, psychological, and social harms. A major physical harm is ketamine-induced ulcerative cystitis, particularly linked to chronic, frequent use. Frequent daily use is also associated with neurocognitive impairment, most robustly deficits in working and episodic memory. Recent studies suggest neurological abnormalities that may underlie these cognitive effects. Many frequent users report trying but failing to stop using ketamine, indicating addiction concerns. Treatment for ketamine-induced ulcerative cystitis should coordinate urologists and addiction specialists. Neurocognitive impairment can negatively impact educational and work achievement and compound addiction. Prevention and harm minimization campaigns are needed to alert young people to these potentially chronic effects.
Addiction
May 1, 1994
Thomas Steele, Una D. Mccann, George A. Ricaurte
295 citations
MDMA (Ecstasy) produces a mix of stimulant and psychedelic effects mediated by brain monoamines, especially serotonin and dopamine. It also shows toxic activity toward brain serotonin neurons in animals, including non-human primates, at doses close to those used by humans. Whether MDMA is neurotoxic in humans remains under investigation, but documented adverse effects include systemic complications and neuropsychiatric consequences involving mood, cognition, and anxiety. Because MDMA use is restricted, retrospective clinical observations are a primary source of human data. This article reviews MDMA's behavioral pharmacology and toxicology to help clinicians recognize MDMA-related syndromes and understand serotonin's role in health and disease.
Addiction
July 1, 1997
Valerie H. Curran, Ross A. Travill
283 citations
Recreational use of MDMA (ecstasy) leads to elevated mood on the day of use but a significant low mood five days later, with some users scoring within the range for clinical depression. Compared to alcohol users, who showed a U-shaped mood curve with the lowest point the day after drinking, MDMA users also had significant impairments on an attentional and working memory task. The findings suggest that weekend MDMA use may cause mid-week depressed mood, possibly due to temporary serotonin depletion, serotonergic neurotoxicity, or psychological factors.
Addiction
December 20, 2006
Robert S. Gable
240 citations
A systematic review and interviews with ceremony participants assessed the acute toxicity and psychological risks of ayahuasca, a brew containing dimethyltryptamine (DMT) and β‐carbolines used in religious ceremonies. No animal models tested ayahuasca's acute toxicity or abuse potential, but separate studies of DMT and harmala alkaloids suggest a lethal human dose is probably over 20 times a typical ceremonial dose. Adverse effects may occur with casual use, especially alongside serotonergic substances. DMT can cause aversive reactions or transient psychotic episodes that resolve within hours. There is no evidence of substantial abuse potential, and long-term psychological benefits are documented when used in a well-established social context. The safety margin is comparable to codeine, mescaline, or methadone.
Addiction
March 24, 2006
Chelsea A. Baylen, Harold Rosenberg
214 citations
A review of 24 studies on the acute subjective effects of MDMA/ecstasy identified a set of effects consistently reported across multiple investigations. The most common effects were emotional (anxiety, depression, closeness, fear, euphoria, calmness) and somatic (nausea/vomiting, bruxism, muscle aches/headache, sweating, numbness, body temperature changes, fatigue, dizziness, dry mouth, increased energy). Only one sexual effect (sexual arousal), one cognitive effect (confused thought), one sensory-perceptual effect (visual changes), one sleep-related effect (sleeplessness), and one appetite-related effect (decreased appetite) were reported in five or more studies. Three factors—time since ingestion, dose level, and gender—influence the acute subjective experience.
Addiction
July 8, 2006
Roland W. Freudenmann, Florian Öxler, Sabine Bernschneider‐reif
201 citations
MDMA was first synthesized by Merck in 1912, but not as an appetite suppressant as commonly claimed. Original documents from Merck's archive show it was an unimportant precursor in a new synthesis for hemostatic substances, patented to evade a competitor's patent. Pharmacological testing occurred in 1927 and 1959, but not in humans. The myth that MDMA was developed as an appetite suppressor likely arose from uncritical copy-paste errors in later literature.
Addiction
February 27, 2006
Euphrosyne Gouzoulis‐mayfrank, Jörg Daumann
189 citations
The popular dance drug ecstasy (MDMA) causes selective and persistent damage to serotonin-producing neurons in laboratory animals. Serotonin regulates many brain functions, so damage could lead to psychiatric, cognitive, and other disorders. This review of studies on ecstasy users finds that, despite major methodological problems, the evidence suggests lasting changes in serotonin transmission, though partial recovery may occur after long-term abstinence. The most consistent finding links heavy ecstasy use with subtle cognitive impairments, especially in memory. However, the evidence is not definitive, and questions about pre-existing traits or polydrug use remain unresolved.
Addiction
July 1, 2001
Sarah Riley, Charlotte James, Danielle Gregory et al.
172 citations
Over 80% of drug users at dance events in Edinburgh had used ecstasy and amphetamine, often weekly and in combination, with over 30% using cocaine and LSD, and over 10% using nitrites, psilocybin, and ketamine. Poly-drug and mixing-drug behaviors were significantly more common than single-drug use. Drugs were primarily accessed through friends. 85% reported mixing drugs and/or alcohol, 35% driving on drugs, 36% having a bad experience, 30% unprotected sex, and 0.9% injecting drugs. Women reported higher consumption than men. The pattern suggests implications for health promotion and criminal policy.
Addiction
July 14, 2009
Caleb J. Banta‐green, Jennifer A. Field, Aurea C. Chiaia‐hernández et al.
161 citations
Wastewater from 96 Oregon municipalities, covering 65% of the state's population, was analyzed for metabolites of cocaine, methamphetamine, and MDMA. Cocaine metabolite levels were significantly higher in urban areas and often undetectable in rural ones. Methamphetamine was present in all communities, with no difference by urbanicity. MDMA was detected in fewer than half the communities, with higher levels in more urban areas. The findings suggest wastewater analysis can measure community drug use patterns and may provide more comprehensive data than traditional surveys.
Addiction
December 1, 2002
Jon C. Cole, Mike Bailey, Harry Sumnall et al.
149 citations
In 2001, ecstasy tablets seized in north-west England contained between 20 and 109 mg of MDMA, with most tablets averaging 60–69 mg. Some tablets also contained MDEA. The most common type, Mitsubishi tablets, spanned the full range of MDMA content. Analysis of 80 samples from a single large seizure of White Dove tablets showed low variation, indicating consistent manufacturing. Comparing these data with UK-wide analyses from 1991 to 2001 shows that the average MDMA content in ecstasy tablets has been declining over the decade. The authors argue that because the amount of MDMA per tablet is dropping, studies of long-term effects and neurotoxicity must account for actual ingested doses.
Addiction
October 1, 1993
Henry David Abraham, Andrew M. Aldridge
140 citations
Lysergic acid diethylamide (LSD) use is linked to panic reactions, prolonged schizoaffective psychoses, and a post-hallucinogen perceptual disorder that can persist for up to 5 years. Evidence does not support claims that hallucinogens cause genetic disorders. Current data confirm earlier findings that LSD can lead to long-lasting psychopathology in vulnerable individuals. A hypothetical long-term molecular mechanism for these adverse effects is proposed.
Addiction
February 20, 2003
Erkki Vuori, John A. Henry, Ilkka Ojanperä et al.
113 citations
Four deaths occurred after people took moclobemide and MDMA ('ecstasy') together. The likely cause of death in each case was serotonin syndrome, a dangerous condition caused by the interaction between the two drugs. None of the victims had a prescription for moclobemide; each apparently took it to boost the effects of MDMA, leading to fatal outcomes. The authors call for warnings against uninformed efforts to enhance the effects of illicit drugs.
Addiction
August 17, 2022
Ofir Livne, Dvora Shmulewitz, Claire Walsh et al.
90 citations
Hallucinogen use in the United States has shifted in opposite directions across age groups since 2002. Among adolescents aged 12–17, use declined, while adults aged 26 and older showed increased use, particularly after 2015. By 2019, over 5.5 million adults aged 18 and older were estimated to have used hallucinogens in the past year. Lysergic acid diethylamide (LSD) use rose across all age groups, while ecstasy use fell among adolescents and adults. Phencyclidine (PCP) use decreased overall and among younger age groups. These trends come from nationally representative survey data spanning 2002 to 2019.
Addiction
August 8, 2006
J. G. Ramaekers, K. P. C. Kuypers, N. Samyn
90 citations
MDMA, a popular recreational drug in Europe, has stimulant-like effects on driving that vary by task. In a double-blind, placebo-controlled crossover study, 18 recreational MDMA users took 75 mg MDMA, 20 mg methylphenidate, or placebo. During the intoxication phase (3–5 hours after dosing), both MDMA and methylphenidate improved road-tracking performance, reducing the standard deviation of lateral position by about 2 cm compared to placebo. However, MDMA impaired car-following performance, causing subjects to overcorrect in response to speed changes of a leading vehicle. No driving impairments were observed during the withdrawal phase (27–29 hours after dosing).
Addiction
February 14, 2011
Kate Morefield, Michael Keane, Peter Felgate et al.
83 citations
Ecstasy pills in recreational settings often contain MDMA, but many also include other drugs like MDEA and methamphetamine. The amount of MDMA per pill varies widely, from 0 to 245 mg. Users typically consume between half a pill and five pills in a session, with total MDMA doses reaching up to 280 mg. Plasma concentrations of MDMA rise with the number of pills consumed and the cumulative dose. Taking multiple pills over several hours leads to sustained high MDMA levels in the blood, exposing the brain to the drug for longer than single-dose studies would suggest.
Addiction
August 1, 2010
Udo Benzenhöfer, Torsten Passie
69 citations
Alexander Shulgin is often called the 'father' of MDMA, but a re-assessment of his original publications and laboratory notebook shows he did not synthesize or try MDMA in 1965 as his book PIHKAL suggests. He learned of its special effects in the mid-1970s, re-synthesized it, and first tried it in September 1976. In 1977 he gave MDMA to psychotherapist Leo Zeff, who then introduced it to other therapists. Shulgin also co-authored the first paper on MDMA's pharmacological action in humans in 1978. These contributions explain why he is sometimes erroneously called the 'father' of MDMA, though he was not the first to synthesize it.
Addiction
August 4, 2009
Linda B. Cottler, Kit Sang Leung, Arbi Ben Abdallah
56 citations
Among 593 people who had used MDMA more than five times in their lives, 15% met criteria for abuse and 59% for dependence under the DSM-IV classification. The diagnostic categories showed moderate test-retest reliability across St. Louis, Miami, and Sydney. The most common dependence criteria were continued use despite knowing it caused physical or psychological problems (87%) and withdrawal (68%). Physically hazardous use was the most prevalent abuse criterion. Seventeen of 19 withdrawal symptoms were reliably reported. Discrepant responses between interviews were mostly due to changing interpretation of questions rather than lying. The pattern of withdrawal symptoms suggests MDMA dependence should be classified separately from other hallucinogens.
Addiction
July 26, 2012
Daniel Wagner, Benjamin Becker, Philip Koester et al.
54 citations
A prospective cohort study followed 109 nearly MDMA-naive subjects for 12 months to determine whether cognitive deficits appear after beginning MDMA use. Twenty-three subjects who used more than 10 MDMA pills (mean 33.6 pills) were compared with 43 subjects who used no illicit drugs besides cannabis. Groups did not differ in age, intelligence, cannabis, alcohol, or other lifestyle confounders. MDMA users showed significant impairments in immediate and delayed recall of a visual paired associates learning task compared with controls, but no differences emerged on other tests of memory, learning, or executive function. The findings suggest MDMA specifically impairs visual paired associates learning, possibly due to serotonergic dysfunction in the hippocampus.
Addiction
July 15, 2005
Rainer Thomasius, Kay Uwe Petersen, P. Zapletalova et al.
54 citations
Current and former ecstasy users show no higher rates of most mental disorders than non-users, except for substance-related disorders. Substance-induced cognitive, affective, and anxiety disorders were more common among ecstasy users than polydrug controls. Lifetime ecstasy dependence occurred in 73% of users. Over half of former users and nearly half of current users met criteria for substance-induced cognitive disorders at testing. Higher lifetime doses of ecstasy predicted cognitive disorders. Pre-existing depression or anxiety did not explain ecstasy use, as these disorders were not more frequent in users. Cognitive problems persisting after more than five months of abstinence may result from MDMA's serotonergic neurotoxicity.
Addiction
June 7, 2023
Katherine M. Keyes, Megan E. Patrick
42 citations
From 2018 to 2021, past-year use of non-LSD hallucinogens (such as psilocybin) among US young adults aged 19–30 doubled from 3.4% to 6.6%, while LSD use remained stable around 4%. Males were nearly twice as likely as females to use non-LSD hallucinogens, and use was lower among Black participants and those without a college-educated parent. The findings suggest growing use of these substances in a population that may be vulnerable to their effects.
Addiction
May 22, 2007
Roberta Pacifici, Piergiorgio Zuccaro, Magı́ Farré et al.
39 citations
People who use both MDMA (ecstasy) and cannabis show long-term changes in immune function, including lower levels of interleukin-2 and higher levels of anti-inflammatory transforming growth factor beta-1, along with fewer total lymphocytes, CD4 cells, and natural killer cells. These immune alterations persisted over one year. Regular users of both drugs had a higher rate of mild infections compared to occasional users and those who used only cannabis or neither drug. Cannabis-only users showed intermediate immune changes. The findings suggest that sustained disruption of immune balance may lead to poorer general health and greater susceptibility to infections.
Addiction
October 10, 2006
Toshihiko Matsumoto, Takayuki Okada
29 citations
A 22-year-old man with no prior mental illness committed a homicide during a severe psychotic state induced by the designer drugs 5-MeO-DIPT and 5-MeO-MIPT, which he purchased online. He ingested unknown quantities of 'Wild Game' and 'Mipty' to enhance sexual pleasure, but within 1.5 hours experienced palpitations, nausea, delusions, visual distortions, and loss of consciousness. Police found him naked and confused 3 hours later; his girlfriend had been killed with a kitchen knife. Laboratory tests confirmed the tryptamine derivatives in his urine and her body; no other substances were detected. Clinical recovery occurred after 17 hours, with amnesia for the event. This is the first reported homicide linked to these drugs, and the authors suggest that simultaneous intake of both analogues may prolong serotoninergic overactivation, causing severe psychosis.
Addiction
January 30, 2025
Theodore Piper, Francesca Small, Michael Kelleher et al.
27 citations
This first systematic review of psychedelic-assisted treatments for alcohol, tobacco, and other substance use disorders examined 37 studies involving 2,035 participants. The best evidence of efficacy came from a phase 2 randomized controlled trial of psilocybin for alcohol use disorder and a phase 2 trial of ketamine for alcohol use disorder. Psilocybin-assisted treatment for alcohol use disorder appears to have the strongest evidence among all major psychedelic-assisted treatments. No serious adverse events were reported across any study. The review recommends that future research report all safety events, identify contraindications, mitigate participant blinding, use factorial designs, and develop a core outcome set.
Addiction
March 19, 2021
Amanda Roxburgh, Bülent Şam, Pirkko Kriikku et al.
27 citations
Between 2011 and 2017, MDMA-related death rates increased in Australia, Finland, Portugal, and Turkey, coinciding with higher MDMA purity and availability. Across 1,400 deaths in Turkey, 507 in Australia, 100 in Finland, and 45 in Portugal, most decedents were young males (81–94% male; median age 24–27.5 years). Drug toxicity was the primary cause in Australia (61%), Finland (70%), and Turkey (60%), while other causes dominated in Portugal (56%). Only 13–25% of deaths were due to MDMA alone; these had significantly higher blood MDMA concentrations than multiple-drug toxicity deaths. Other drugs commonly detected included stimulants and alcohol in Australia and Finland, benzodiazepines and opioids in Finland, and synthetic cannabinoids and cannabis in Turkey.
Addiction
January 11, 2024
Nicolas Garel, Steven Tate, Kristin Nash et al.
23 citations
Hallucinogen-related emergency department visits in California rose 54% from 2016 to 2022 (2260 to 3476 visits), while alcohol-related visits fell 20% and cannabis-related visits rose 15%. Hallucinogen-related hospitalizations increased 55% (2556 to 3965), compared with a 1% increase for both alcohol and cannabis. These trends were statistically different from those for alcohol and cannabis. The absolute numbers remain small, but the relative increase is large.