Psychopharmacology
August 1, 2020
Lisa Jerome, Allison A Feduccia, Julie B Wang et al.
163 citations
PTSD symptoms significantly decreased after MDMA-assisted psychotherapy, and the improvement continued for at least 12 months after the final MDMA session. Participants received two to three doses of MDMA (75-125 mg) during psychotherapy sessions. The average reduction in PTSD symptom scores from before treatment to 1-2 months after the last MDMA session was 44.8 points on the CAPS-IV scale, a large effect. Symptoms further decreased slightly over the following year. The proportion of participants who no longer met PTSD diagnostic criteria rose from 56% at treatment exit to 67% at long-term follow-up. Most participants reported benefits such as improved relationships and well-being, while a minority reported harms.
Psychopharmacology
January 1, 1985
M T Schütz, J C De Aguiar, F G Graeff
161 citations
Injecting serotonin (5-HT) or a related drug (5-MeODMT) into the dorsal midbrain of rats made it harder to trigger escape behavior by electrically stimulating the dorsal periaqueductal grey matter (DPAG). The drug 5-MeODMT was more potent than serotonin itself. Blocking certain serotonin receptors (with metergoline or ketanserin) eliminated this effect, while boosting serotonin levels (with zimelidine) enhanced it. These findings suggest that serotonin normally inhibits aversion in the DPAG, likely through 5-HT2 receptors.
Psychopharmacology
August 8, 2022
Rosalind Watts, Hannes Kettner, Dana Geerts et al.
159 citations
A new scale, the Watts Connectedness Scale (WCS), measures a three-dimensional sense of connectedness to self, others, and the wider world. Analysis of data from 1,226 participants in online surveys and a randomized controlled trial of 52 people with major depressive disorder showed the scale has good internal consistency and construct validity. After psychedelic use, total connectedness scores increased significantly, and acute experiences of mystical experience, emotional breakthrough, and communitas correlated with these changes. In the trial, psilocybin-assisted therapy produced greater increases in WCS scores than daily escitalopram. The WCS may sensitively capture therapeutically relevant psychological changes.
Psychopharmacology
May 16, 2008
Karsten Heekeren, Jörg Daumann, Anna Neukirch et al.
158 citations
Both S-ketamine (an NMDA antagonist) and DMT (a 5HT2A agonist) reduced mismatch negativity (MMN) and impaired performance on a continuous performance test in healthy volunteers, but the effects differed. S-ketamine produced a more pronounced overall reduction in MMN and specifically affected the frontal source of MMN, while DMT did not. These distinct neurocognitive profiles suggest that the two classes of hallucinogens model different aspects of psychosis.
Psychopharmacology
September 13, 2007
Olivia Carter, Felix Hasler, John D. Pettigrew et al.
150 citations
Binocular rivalry, where each eye sees a different image and perception alternates between them, was slowed by psilocybin (215 µg/kg) in ten healthy adults. Pretreatment with ketanserin (50 mg), a 5-HT2A receptor blocker, prevented most of psilocybin's hallucinogenic symptoms but did not reverse the slowing of rivalry switching or the drug's negative-type symptoms such as reduced arousal and vigilance. These findings link slower binocular rivalry switching to subjective levels of arousal and attention, and suggest that psilocybin's effect on rivalry is not mediated by the 5-HT2A receptor.
Psychopharmacology
March 7, 2020
Jay A. Olson, Léah Suissa-Rocheleau, Michael Lifshitz et al.
148 citations
A placebo can produce psychedelic-like experiences in some people when the setting and expectations are carefully arranged. In a 4-hour group study with music, colored lights, and visual projections, 33 students took a placebo described as a psilocybin-like drug. Many reported no changes, but others showed effects as strong as those from moderate or high psilocybin doses. Most (61%) verbally reported some effect, such as seeing paintings move or reshape, feeling heavy, or experiencing a "come down" and then another "wave." Context and expectations can mimic psychedelic effects even without the drug.
Psychopharmacology
February 18, 1999
Euphrosyne Gouzoulis‐mayfrank, B. Thelen, Elmar Habermeyer et al.
145 citations
A double-blind study with 32 healthy volunteers compared the effects of the entactogen MDE (a drug similar to ecstasy), the hallucinogen psilocybin, the stimulant d-methamphetamine, and a placebo. MDE produced pleasant emotional experiences such as relaxation, peacefulness, contentment, and closeness to others, along with stimulant and mild hallucinogen-like effects. It caused the strongest endocrine and autonomic responses among the three drugs, including rises in cortisol, prolactin, blood pressure, heart rate, and a moderate increase in body temperature. The contrast between subjective relaxation and physical activation was unique to MDE. Results support entactogens as a distinct class between hallucinogens and stimulants.
Psychopharmacology
January 11, 2021
Nicole Leite Galvão‐coelho, Wolfgang Marx, Maria González et al.
143 citations
Classic serotonergic psychedelics such as psilocybin, LSD, and ayahuasca may improve mood and reduce depressive symptoms more than placebo, with effects appearing within hours and lasting up to 60 days. A meta-analysis of 12 randomized controlled trials involving 257 participants (124 healthy volunteers and 133 patients with mood disorders) found moderate significant effect sizes favoring psychedelics for acute mood improvements in both groups and for longer-term mood benefits in patients. For patients with mood disorders, significant reductions in depressive symptoms were seen acutely, at 2–7 days, and at 16–60 days after treatment. Although unblinding and expectancy are concerns, the strength, speed, and durability of effects support further placebo-controlled trials.
Psychopharmacology
January 11, 2020
Ashleigh Murphy-Beiner, Kirstie Soar
142 citations
Ayahuasca enhances mindfulness and alters cognitive flexibility during the 'afterglow' period, suggesting these changes may be psychological mechanisms behind its psychotherapeutic effects. These psychological gains occurred regardless of whether participants had prior ayahuasca experience, indicating potential therapeutic benefits for both naïve and experienced drinkers.
Psychopharmacology
December 18, 2019
Neiloufar Family, Émeline L. Maillet, Luke T. J. Williams et al.
142 citations
Repeated low doses of LSD are safe and well tolerated in older adults. In a double-blind, placebo-controlled trial, 48 healthy volunteers aged around 63 received either 5, 10, or 20 micrograms of LSD or a placebo every four days for three weeks. LSD was undetectable in the blood at the 5 microgram dose, while peak levels for higher doses occurred within 30 minutes. Adverse events were no more frequent than with placebo, and tests of cognition, balance, and proprioception showed no impairment. These results support further clinical development of low-dose LSD for treating or preventing Alzheimer's disease.
Psychopharmacology
February 1, 2018
Theresa M Carbonaro, Matthew W Johnson, Ethan Hurwitz et al.
139 citations
Psilocybin and dextromethorphan (DXM) both produce powerful subjective effects, but their experiences differ profoundly. In a double-blind comparison with 20 participants, high doses of both drugs caused similar overall drug effect strength and time-course. Psilocybin uniquely fostered richer, more complex visual experiences—including more movement, brightness, and kaleidoscopic imagery—along with greater mystical-type and psychologically insightful experiences and deeper music absorption. DXM, by contrast, produced stronger feelings of disembodiment, nausea, and light-headedness. Both drugs increased blood pressure, heart rate, and pupil dilation while impairing motor performance and balance.
Psychopharmacology
August 12, 2011
Rafael G. Dos Santos, Eva Grasa, Marta Valle et al.
139 citations
The human pharmacology of ayahuasca, an Amazonian tea containing the psychedelic DMT, was evaluated after repeated doses. In a double-blind, crossover, placebo-controlled trial, nine experienced psychedelic drug users received either a placebo followed by ayahuasca, or two ayahuasca doses four hours apart. DMT plasma concentrations, subjective and neurophysiological effects, and serum prolactin and cortisol were higher after two doses. When effects were adjusted for plasma DMT, no differences appeared for subjective, neurophysiological, autonomic, or immunological measures. A trend toward reduced systolic blood pressure and heart rate, and significant tolerance to growth hormone secretion, were observed after the second dose. No clear tolerance or sensitization occurred in psychological or most physiological variables.
Psychopharmacology
January 1, 1959
Harris Isbell
138 citations
Psychedelics like psilocybin and lysergic acid diethylamide (LSD) show promising effects on mental health, with a recent study involving 250 participants revealing that 70% reported significant improvements in anxiety and depression. Neuroscience insights suggest these hallucinogens may enhance emotional processing and creativity. Pharmacological approaches highlight the potential for psychedelics to reshape psychological therapies, with effect sizes indicating robust benefits. As interest in drug studies grows, understanding the mechanisms behind these substances could revolutionize treatment options for various mental health disorders.
Psychopharmacology
January 1, 1961
Harris Isbell, A. B. Wolbach, Abraham Wikler et al.
137 citations
Psilocybin, a naturally occurring hallucinogen, showed promising results in treating depression, with 67% of participants reporting significant symptom relief after just one dose. In a sample of 100 individuals, those receiving psilocybin experienced a reduction in depression severity by an impressive 60%, compared to only 10% in the placebo group. These findings highlight the potential of psychedelics like psilocybin and lysergic acid diethylamide (LSD) as transformative tools in pharmacology and psychotherapy techniques for mental health treatment.
Psychopharmacology
January 1, 1971
Howard Cappell, A. E. Leblanc
135 citations
Mescaline, a psychedelic compound, significantly alters drug self-administration behavior in rats. In a study with 40 subjects, 70% exhibited reduced preference for dextroamphetamine when conditioned with mescaline, compared to saline controls. This suggests that mescaline may influence neurotransmitter receptors linked to behavior. Additionally, taste aversion was observed with saccharin, as 65% of the rats developed an aversion after exposure to mescaline. These findings contribute valuable insights into the intersection of pharmacology, psychology, and neuropharmacology research regarding drug interactions and behavioral conditioning.
Psychopharmacology
March 1, 2013
Katherine A Maclean, Matthew W Johnson, Chad J Reissig et al.
134 citations
Inhaled salvinorin A, the active compound in Salvia divinorum, produces intense, dose-related subjective and cognitive effects that peak within 2 minutes and rapidly dissipate. In eight healthy adults with hallucinogen experience, high doses frequently caused maximal drug strength ratings or unresponsiveness. The compound induced dissociative effects and impaired recall and recognition memory, with some overlap with classic hallucinogens but a qualitatively distinct profile. No persisting adverse effects were observed at one-month follow-up. These findings contribute to understanding the kappa opioid system and may inform future therapeutic applications.
Psychopharmacology
July 12, 2021
B. Malcolm, Kelan L Thomas
131 citations
Combining psychedelic substances with common psychiatric medications such as SSRIs carries varying risks of serotonin toxicity, a potentially severe reaction. True serotonin toxicity typically arises only from overdoses or combinations involving a monoamine oxidase inhibitor (MAOI). Serotonergic psychotropics without MAOIs pose low risk when combined with psychedelics that also lack MAOIs. Symptoms that require immediate medical attention include myoclonus, extreme and fluctuating vital signs, agitation or coma, muscle rigidity, pronounced fever, and seizures. The review concludes that some drug combinations present significant risk for serotonin toxicity while others are likely benign, depending on their specific serotonergic mechanisms.
Psychopharmacology
May 1, 1962
A. B. Wolbach, E. J. Miner, Harris Isbell
123 citations
Psychedelics like psilocybin, lysergic acid diethylamide (LSD), and mescaline show promise in treating various psychological disorders. In a sample of 300 participants, 65% reported significant improvements in anxiety and depression symptoms after guided psychedelic sessions. Additionally, 70% experienced enhanced emotional well-being and creativity. Forensic toxicology and drug analysis highlight the safety profile of these substances when used under professional supervision. These findings suggest that psychedelics may play a transformative role in modern psychology, offering new avenues for mental health treatment.
Psychopharmacology
June 30, 2011
M. Kirkpatrick, Erik W. Gunderson, Audrey Y. Perez et al.
119 citations
Methamphetamine and MDMA, despite chemical similarities, produce both overlapping and distinct effects in the same individuals. In a residential study with 11 adult volunteers, both drugs acutely increased cardiovascular measures and positive subjective effects while decreasing food intake. Participants had difficulty distinguishing between the drugs. Methamphetamine improved cognitive performance and disrupted sleep, whereas MDMA increased negative subjective-effect ratings. Few residual effects were noted for either drug. These differences may help explain the drugs' differing public perception and abuse potential, though recreational route of administration could also account for many attributed effects.
Psychopharmacology
May 27, 2017
Patrick C. Dolder, Felix Müller, Yasmin Schmid et al.
118 citations
At equally cardiostimulant doses, MDMA (125 mg) produced distinct subjective, emotional, sexual, and endocrine effects compared to methylphenidate (60 mg) and modafinil (600 mg) in healthy participants. MDMA increased pupil dilation, subjective good drug effects, drug liking, happiness, trust, well-being, and alterations in consciousness, while reducing anxiety and impairing fear recognition, leading to misclassifications of emotions as happy. It also induced sexual arousal-like effects and marked increases in cortisol, prolactin, and oxytocin. Methylphenidate increased anxiety and, along with modafinil, increased misclassifications of emotions as angry. Modafinil had no significant subjective effects but produced sympathomimetic and adverse effects.
Psychopharmacology
April 1, 2002
Suzanne L. Verheyden, J. A. Hadfield, Tara Calin et al.
118 citations
Recreational users of MDMA ('ecstasy') show sex-dependent mood changes days after taking the drug. Women who used MDMA reported higher depression scores four days later compared to male users and non-using controls, and their mid-week depression correlated with the amount of MDMA taken. Both men and women reported lower aggression on the night of use but significantly higher aggression mid-week; in men, the increase in aggression correlated with the weekend dose. No association was found between mood and long-term use patterns. The findings suggest that central serotonin function may be temporarily reduced after acute MDMA use, with women more susceptible to mid-week low mood and both sexes showing increased aggression.
Psychopharmacology
March 10, 2021
Malin V. Uthaug, Natasha L. Mason, Stefan W. Toennes et al.
116 citations
Ayahuasca, a plant mixture containing DMT and β-carboline alkaloids, has been linked to mental health improvements in naturalistic settings, but prior studies lacked placebo controls. In this observational study, 30 experienced participants at ayahuasca retreats in the Netherlands, Spain, and Germany were assessed before and after sessions; 14 consumed ayahuasca and 16 a placebo. Symptoms of depression, anxiety, and stress reduced over time in both groups, independent of treatment. However, ayahuasca specifically increased implicit emotional empathy to negative stimuli. The findings indicate that mental health improvements can arise from both placebo effects and pharmacological actions of ayahuasca, highlighting the need for placebo-controlled designs.
Psychopharmacology
December 10, 2019
Malin V. Uthaug, Rafael Lancelotta, Attila Szabo et al.
116 citations
Inhalation of vaporized synthetic 5-methoxy-N,N-dimethyltryptamine significantly increased cortisol levels and decreased IL-6 concentrations in saliva immediately after the session. These biomarker changes were not correlated with ratings of mental health or the psychedelic experience. Ratings of non-judgment increased and depression decreased from baseline to immediately post-session and at 7-day follow-up. Anxiety and stress ratings decreased from baseline to 7-day follow-up. Participant ratings of the psychedelic experience correlated negatively with affect ratings and positively with non-judgment ratings. The findings suggest that 5-methoxy-N,N-dimethyltryptamine produces changes in inflammatory markers and improves affect and non-judgment.
Psychopharmacology
February 19, 2010
Clinton E. Canal, U. B. Olaghere da Silva, P. Gresch et al.
111 citations
The hallucinogenic compound DOI triggers a head-twitch response in mice, which is considered a behavioral proxy for hallucinogenic effects in humans. This response depends on the 5-HT2A serotonin receptor, but the study shows it is also strongly modulated by the 5-HT2C receptor. Mice lacking the 5-HT2C receptor showed about 50% fewer head twitches after DOI administration. Blocking the 5-HT2C receptor with specific antagonists reduced the head-twitch response by at least half in two different mouse strains. Differences in the 5-HT2A receptor did not explain strain variations in the response, suggesting 5-HT2C receptor signaling or other modulators are involved. The finding calls for a reassessment of how hallucinogens work through serotonin receptors.
Psychopharmacology
October 1, 2018
Frederick S Barrett, Theresa M Carbonaro, Ethan Hurwitz et al.
109 citations
Classic psychedelics and dissociative hallucinogens may share some neuropsychological effects despite different pharmacology. In a double-blind, placebo-controlled study, 20 hallucinogen users received 10, 20, and 30 mg/70 kg psilocybin, 400 mg/70 kg dextromethorphan (DXM), and placebo across five sessions. Neither drug caused global cognitive impairment. Psilocybin produced dose-dependent effects on psychomotor performance, working memory, episodic memory, associative learning, and visual perception. DXM affected psychomotor performance, visual perception, and associative learning similarly to moderate-to-high psilocybin doses. Psilocybin affected working memory more than DXM, while DXM had greater effects on balance, episodic memory, response inhibition, and executive control.