Human Psychopharmacology Clinical and Experimental
December 1, 2001
A. C. Parrott
349 citations
MDMA (Ecstasy) is an illegal drug that increases serotonin and other neurotransmitter activity, producing euphoria, hyperactivity, and hyperthermia, especially in hot, crowded settings. Around 80% of users experience rebound depression and lethargy days after use. Repeated use causes tolerance and, in animals, serotonergic neurotoxicity. In humans, heavy users show reduced serotonin markers and deficits in memory, cognition, sleep, appetite, and sexual interest, which persist long after stopping use, suggesting permanent neuropharmacological damage.
Human Psychopharmacology Clinical and Experimental
April 7, 2015
Caoimhe M. Coyle, Keith R. Laws
279 citations
Ketamine infusion produces a significant antidepressant effect in people with major depressive disorder and bipolar disorder, with effects appearing within 4 hours and lasting up to 7 days after a single dose. Repeated infusions produce larger effects than single infusions at 4 hours, 24 hours, and 7 days. The proportion of male participants predicted a stronger antidepressant response at 7 days. Peak response time may differ by diagnosis: 24 hours for major depressive disorder and 7 days for bipolar disorder. Results from studies at 12–14 days did not reach significance. Most published studies used pre–post comparisons; more placebo-controlled studies are needed.
Human Psychopharmacology Clinical and Experimental
June 1, 2006
Sean P. Barrett, Christine Darredeau, Robert O. Pihl
276 citations
Among 149 university students who use drugs, alcohol, tobacco, and cannabis are frequently used together and with other substances. When alcohol is taken with cannabis, psilocybin, MDMA, cocaine, amphetamine, methylphenidate, or LSD, alcohol is typically consumed first. People drink more alcohol when they also use cocaine or methylphenidate than when they drink alone. Tobacco smoking increases above usual rates when used with alcohol, cannabis, psilocybin, MDMA, cocaine, amphetamine, LSD, or methylphenidate. Cannabis use patterns do not systematically relate to other substances. The findings indicate that the way a substance is used often depends on what other substances are taken at the same time.
Human Psychopharmacology Clinical and Experimental
December 1, 2001
Matthias E. Liechti, Franz X. Vollenweider
243 citations
The psychological effects of MDMA (Ecstasy) largely depend on the release of serotonin (5-HT), while its stimulant-like euphoric mood effects relate in part to dopamine D2 receptor stimulation, and its mild hallucinogen-like perceptual effects are due to serotonergic 5-HT2 receptor stimulation. In 44 healthy volunteers, the selective serotonin reuptake inhibitor citalopram markedly reduced most subjective effects of MDMA, including positive mood, extraversion, and self-confidence, and also attenuated cardiovascular and adverse effects. The D2 antagonist haloperidol selectively reduced MDMA-induced positive mood but had no effect on other subjective or cardiovascular responses. The 5-HT2 antagonist ketanserin selectively reduced MDMA-induced perceptual changes and emotional excitation.
Human Psychopharmacology Clinical and Experimental
July 1, 2013
A. C. Parrott
184 citations
MDMA, initially considered a novel psychoactive substance with low abuse potential due to loss of efficacy, is now understood to cause widespread neuropsychobiological damage. Recreational users show a pattern of increasing doses and deteriorating cost-benefit ratios. MDMA elevates body temperature and thermal stress, and can increase cortisol levels by 800% in dance clubbers. It can be extremely euphoric but also intensifies negative moods. The drug causes apoptosis and has been investigated for cancer therapy due to anti-lymphoma properties. Users exhibit deficits in memory, higher cognition, problem solving, and social intelligence, while basic cognitive skills remain intact.
Human Psychopharmacology Clinical and Experimental
October 1, 2003
171 citations
Regular MDMA users report both positive and negative psychological effects. Among 466 regular users, acute effects include positive and negative impacts on mental health and physical effects. Between sessions, 83% experienced low mood and 80% impaired concentration. Long-term effects include tolerance (59%), impaired concentration (38%), depression (37%), and feeling more open toward people (31%). Factors such as age, gender, extent of MDMA use, and use of cocaine or amphetamine influence these effects. Users' main concern about stopping MDMA is its long-term effects on mental health.
Human Psychopharmacology Clinical and Experimental
July 12, 2002
A. C. Parrott, Tom Buchanan, Andrew Scholey et al.
163 citations
Depression, memory problems, anxiety, mood fluctuation, poor concentration, infections, tremors/twitches, and weight loss are all more common among people who have used Ecstasy more often. In a survey of 282 Ecstasy users, memory problems attributed to the drug were reported by 19% of novice users (1–9 occasions), 52% of moderate users (10–99 occasions), and 73% of heavy users (100+ occasions). The incidence of psychobiological problems attributed to Ecstasy use increases directly with the number of times it has been used.
Human Psychopharmacology Clinical and Experimental
May 1, 1997
D. Davison, A. C. Parrott
136 citations
Twenty recreational drug users described the psychological and physiological effects of MDMA. On the drug, they reported increased elation, agreeableness, energy, mental confusion, faster heart rate, feeling hot, sweating, dehydration, dilated pupils, and tight jaw. Coming off the drug led to lethargy, moodiness, insomnia, depression, irritability, and paranoia. 25 percent of the sample reported bad trips. Chronic tolerance was not apparent, but acute tolerance was evident, with a necessary period between doses to maintain effectiveness, which may help explain MDMA's low addiction potential.
Human Psychopharmacology Clinical and Experimental
September 19, 2003
Fabrizio Schifano, Adenekan Oyefeso, John Corkery et al.
93 citations
Between August 1996 and April 2002, 202 deaths related to ecstasy use occurred in England and Wales, with a steady annual increase. Most victims were young men: the male-to-female ratio was 4:1, and three-quarters were under age 29. In 17% of cases ecstasy was the only drug involved; the rest involved other substances, most often alcohol, cocaine, amphetamines, and opiates. MDMA was detected in 86% of cases and MDA in 13%; MDEA and PMA caused single deaths. This is the largest sample of ecstasy-related deaths reported at the time. The authors propose possible explanations for the rising trend and a rationale for the observed polypharmacy combinations.
Human Psychopharmacology Clinical and Experimental
September 25, 2007
Konstantine K. Zakzanis, Zachariah Campbell, Diana Jovanovski
87 citations
A meta-analysis of studies on MDMA users found small-to-medium cognitive impairments across all tested domains, with learning and memory most affected. Greater lifetime MDMA consumption was linked to worse performance on attention, concentration, learning, and memory tasks.
Human Psychopharmacology Clinical and Experimental
December 1, 2001
Kirstie Soar, John Turner, A. C. Parrott
80 citations
A review of psychiatric case studies from the last 10 years finds that MDMA (Ecstasy) is strongly linked to the onset of psychological disorders and persistent psychiatric symptoms. Only 24% of patients had a previous psychiatric history, and 34% had a psychiatric illness among first-degree relatives. The substantial proportion of patients without such history, along with the temporal relationship between MDMA use and recurring symptoms, suggests a causal role of the drug. Supporting evidence from non-clinical samples shows that Ecstasy users have higher scores on SCL-90 subscales compared to non-users, with heavier users showing more pathology.
Human Psychopharmacology Clinical and Experimental
December 1, 2001
Jörg Daumann, Susanna Pelz, Stefanie Becker et al.
77 citations
Recreational Ecstasy (MDMA) is known to damage serotonin neurons in animals, and human studies link it to memory problems. This investigation examined psychological profiles of 28 abstinent Ecstasy users who also used cannabis, compared with equal-sized groups of cannabis-only users and non-users. Ecstasy users reported higher impulsiveness, anxiety, sensation seeking, somatic complaints, obsessive-compulsive behavior, and psychoticism. However, after accounting for cannabis use, most group differences were no longer statistically significant. The findings suggest that psychological problems in Ecstasy users are closely tied to concomitant cannabis use, making them less reliable indicators of Ecstasy-related neurotoxic damage than cognitive deficits.
Human Psychopharmacology Clinical and Experimental
May 1, 2017
Daniel Martins, Monica J. Barratt, Cristiana Vale Pires et al.
76 citations
At the 2014 Boom Festival in Portugal, a drug-checking service analyzed 245 samples that users believed to be LSD. Only 67.3% actually contained LSD alone; 24.1% contained another psychoactive substance instead, including 11.4% that were DOx derivatives and 9.8% that were 25x-NBOMe derivatives. Among users who received unexpected results, 74.2% said they did not intend to consume the drug they actually had. After alerts were disseminated on the second day, a larger proportion of all tests conducted were for LSD compared to the 2012 festival, where no such alert was issued. The authors suggest these findings support integrated drug-checking services in party settings.
Human Psychopharmacology Clinical and Experimental
May 5, 2004
76 citations
People who currently use MDMA or have used it in the past show impairments in verbal working memory, specifically on a computation span task, compared to non-users. Current users also show deficits on a reading span task. The impairment on computation span persists even after statistically controlling for the use of cannabis and other drugs, suggesting MDMA may have a specific effect on certain executive functions.
Human Psychopharmacology Clinical and Experimental
July 10, 2007
Keith R. Laws, Joy Kokkalis
75 citations
A meta-analysis of 26 studies found that recreational ecstasy use is associated with moderate to large impairments in memory. Short-term memory showed a moderate deficit, while long-term memory showed a large deficit; the difference between these two types was not significant. Verbal memory was strongly impaired, significantly more than visual memory, which showed only a small impairment. Visual memory problems may be partly due to concurrent cannabis use. The total number of ecstasy tablets consumed over a lifetime did not predict memory performance, suggesting that other factors may be more important.
Human Psychopharmacology Clinical and Experimental
May 9, 2001
Thomas Heffernan, Jonathan Ling, Andrew Scholey
57 citations
Regular ecstasy users report more everyday memory lapses, specifically in remembering to do things in the future (prospective memory), compared to non-users. Thirty regular ecstasy users (taking the drug 10 or more times per month) and 31 ecstasy-free controls completed the Prospective Memory Questionnaire, which measures self-rated errors in short-term habitual, long-term episodic, and internally cued prospective memory. Ecstasy users reported significantly more errors across all three aspects, even after accounting for other drug use. No differences were found in the use of memory aids. These findings suggest prospective memory dysfunction may relate to serotonergic and frontal lobe deficits in chronic MDMA users.
Human Psychopharmacology Clinical and Experimental
December 1, 2001
Liesbeth Reneman, Jan Booij, Charles B.l.m. Majoie et al.
50 citations
Human users of MDMA (Ecstasy) may be at risk of developing MDMA-induced neuronal injury. Previously, no methods were available for directly evaluating neurotoxic effects in the living human brain, but the development of in vivo neuroimaging tools has begun to provide insights. This review highlights contributions of brain imaging studies on the potential neurotoxic effects of MDMA and functional consequences. An overview of PET, SPECT, and MR spectroscopy studies shows evidence of neuronal injury in MDMA users. Different neuroimaging tools have investigated potential functional consequences of MDMA-induced 5-HT neurotoxic lesions. Brain imaging will play a crucial role in understanding MDMA's short- and long-term effects in the human brain.
Human Psychopharmacology Clinical and Experimental
January 1, 2020
Patricia Acosta, Joseph J. Palamar
44 citations
Interviews with 39 adults who had used psychedelic phenethylamines and tryptamines revealed the subjective effects of 36 different compounds. 2C-B was the most commonly used phenethylamine and was often described as more favorable than other 2C series drugs, with effects comparable to MDMA and LSD. NBOMe effects were generally unfavorable, and DOx effects were often reported as lasting 12 to 36 hours, which was considered too long. Among tryptamines, 4-AcO-DMT was most prevalent and was often described as mimicking psilocybin. These findings can inform education, prevention, and harm reduction efforts.
Human Psychopharmacology Clinical and Experimental
February 17, 2022
Edward James, Joachim Keppler, Ben Sessa et al.
41 citations
Ayahuasca and its active compound DMT show potential for treating depression, addictions, PTSD, anxiety, and certain immune system conditions. These substances bind to multiple brain receptors, including serotonergic, glutaminergic, and sigma-1 receptors, and affect BDNF expression and the dopamine system. Subjective effects correspond to increased delta and theta brain waves in the amygdala and hippocampus, decreased alpha waves in the default mode network, and activation of visual brain regions. Although biological and consciousness-based models attempt to explain these effects, evidence remains insufficient for firm conclusions. More research is needed to clarify mechanisms and develop accessible treatments, with recommended collaboration between healthcare researchers and Amazonian practitioners.
Human Psychopharmacology Clinical and Experimental
June 14, 2012
Cecilie Löe Licht, M.v. Christoffersen, Mads Okholm et al.
40 citations
Among 98 Danish users of MDMA (Ecstasy) and hallucinogens, simultaneous use of multiple psychoactive substances was common. Participants had tried an average of 12.6 substances in their lifetime. MDMA was frequently combined with amphetamines (69%), hallucinogens (56%), and cocaine (47%). Alcohol and cannabis were used before, during, and after MDMA, LSD, and psilocybin, while amphetamines were typically taken before these drugs. Users preferred specific combinations to enhance or counteract effects. At their last recalled use, MDMA was taken with an average of 2.1 other substances in 32 different combinations.
Human Psychopharmacology Clinical and Experimental
August 19, 2021
Elisabet Domínguez‐clavé, Joaquim Soler, Matilde Elices et al.
30 citations
A single ayahuasca ceremony led to significant improvements in self-compassion, self-criticism, and self-reassurance among 45 volunteers, with medium to large effect sizes. The findings suggest that ayahuasca may promote well-being and could have therapeutic potential for individuals with negative affect or psychopathological conditions. Most participants had used ayahuasca before. Large, controlled studies are needed to confirm these results.
Human Psychopharmacology Clinical and Experimental
June 23, 2020
Edward James, Thomas L Robertshaw, Mathew Hoskins et al.
29 citations
Psilocybin-assisted psychotherapy shows promise for treating specific psychiatric conditions, with mystical-type experiences linked to therapeutic benefits and long-term improvements in mental outlook. This narrative review summarizes current research on quantifying such experiences and their subjective effects. Recent studies clarify some pharmacological actions of psychedelics, but neurological similarities and differences between spontaneous and drug-induced mystical experiences remain poorly understood. Applicability to modern clinical settings is assessed, and potential novel uses include positive psychology interventions in healthy individuals. Since 2006, significant progress has been made, but more work is needed on neuromechanistic processes and clinical applicability. Funding issues, legal concerns, and socio-cultural resistance counterbalance experimental evidence.
Human Psychopharmacology Clinical and Experimental
March 1, 2012
Mark Wetherell, Katie Atherton, Jessica Grainger et al.
25 citations
Recreational use of cannabis and MDMA, beyond the period of intoxication, can negatively influence psychological responses to a multitasking stressor. In three studies, cannabis users became less alert and content after acute stress, while MDMA users became less calm. Unexpectedly, the stressor increased calmness ratings in cannabis users. Both cannabis and MDMA users reported needing more resources to complete the multitasking framework compared to controls. These findings suggest that such drug use may impair real-life situations that place high demands on cognitive resources.
Human Psychopharmacology Clinical and Experimental
September 1, 1997
A. C. Parrott, Marta Stuart
24 citations
Twenty-one recreational polydrug users aged 17–34 reported their typical feeling states while on MDMA (Ecstasy), LSD, and amphetamine using a modified Profile of Mood States questionnaire. For three mood factors, MDMA produced intermediate effects: feelings of energy, confidence, and clearheadedness were highest under amphetamine, lowest on LSD, and intermediate after Ecstasy. However, MDMA's mood profile was more unique in other respects, with significantly higher feelings of elation, agreeableness, and composure than the other two drugs.
Human Psychopharmacology Clinical and Experimental
February 2, 2022
Rafael G. Dos Santos, Juliana Mendes Rocha, Giordano Novak Rossi et al.
20 citations
A post-hoc analysis of two small randomized placebo-controlled trials measured endocannabinoid (anandamide, AEA; 2-arachidonoylglycerol, 2-AG) plasma levels in healthy volunteers and in volunteers with social anxiety disorder (SAD) after a single oral dose of ayahuasca or placebo. In the SAD group, ayahuasca intake was associated with a significant difference in AEA concentrations over time, and near-significant increases in AEA were observed at 90 and 240 minutes after intake. No definitive conclusions could be drawn due to high interindividual variability and small sample sizes. Larger studies are needed to clarify ayahuasca's effects on the endocannabinoid system.