Journal of Psychopharmacology
August 31, 2016
Theresa M. Carbonaro, Matthew P. Bradstreet, Frederick S. Barrett et al.
541 citations
In a survey of 1,993 people who recalled their worst 'bad trip' after taking psilocybin mushrooms, 39% ranked it among the top five most challenging experiences of their lives. Eleven percent put themselves or others at risk of physical harm, with factors such as higher dose, longer duration, and lack of physical comfort or social support increasing that risk. About 2.6% acted aggressively and 2.7% needed medical help. Among those whose experience was more than a year prior, 7.6% sought treatment for lasting psychological symptoms, with three cases linked to enduring psychotic symptoms and three to attempted suicide. Despite difficulties, 84% reported benefiting from the experience. The incidence of risky behavior or lasting distress is very low when psilocybin is given in controlled laboratory settings.
Brain Research Bulletin
April 30, 2016
Theresa M. Carbonaro, Michael B. Gatch
258 citations
N,N-dimethyltryptamine (DMT) is an indole alkaloid found in plants and animals, known for producing brief, intense psychedelic effects. Evidence suggests endogenous DMT may act as a neurotransmitter in the periphery and central nervous system. This review covers recreational use, potential endogenous roles, pharmacokinetics, mechanisms of action, clinical uses, and adverse effects. DMT appears to have limited neurotoxicity and few adverse effects, except for intense cardiovascular effects when given intravenously in large doses. It may be a useful experimental tool for exploring brain function and a clinical tool for treating anxiety and psychosis.
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
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.
Journal of Psychopharmacology
February 20, 2021
Albert Garcia‐romeu, Frederick S. Barrett, Theresa M. Carbonaro et al.
101 citations
Psilocybin, a naturally occurring psychedelic, shows promise for treating mood and substance use disorders when given in structured settings. Most trials have adjusted the dose by body weight, but fixed dosing is simpler and cheaper. Analyzing data from ten previous studies (total 288 participants) that used weight-adjusted doses of 20 or 30 mg per 70 kg, or a fixed dose approximating 25 mg, no significant associations emerged between body weight or sex and the subjective effects (mystical, challenging, or intensity). Across body weights from 49 to 113 kg, body weight did not affect psilocybin's subjective effects, suggesting fixed dosing is as effective and more practical than weight-adjusted dosing.
Psychopharmacology
July 2, 2014
Theresa M. Carbonaro, Amy J. Eshleman, Michael J. Forster et al.
67 citations
The 5-HT2A receptor plays a major role in mediating the effects of the hallucinogens DMT and DiPT. A 5-HT2A receptor inverse agonist fully blocked the discriminative stimulus effects of DMT but only partially blocked those of DiPT. A 5-HT2C receptor antagonist partially attenuated DiPT's effects but minimally affected DMT. An mGluR2/3 agonist produced potent but partial blockade of DMT's effects, while an mGluR2/3 antagonist facilitated the effects of both compounds. Both DMT and DiPT induced head twitches, with DiPT producing more, and these were blocked by a 5-HT2A receptor inverse agonist. DiPT acted as a low-potency full agonist at the 5-HT2C receptor in vitro. The findings suggest that 5-HT2C and mGluR2 receptors modulate the effects of these tryptamine hallucinogens to some degree.
Psychopharmacology
August 1, 2020
Theresa M. Carbonaro, Matthew W Johnson, Roland R. Griffiths
51 citations
Psilocybin produces stronger positive subjective effects than dextromethorphan (DXM) at comparable peak drug strength, which may explain its higher rates of non-medical use. In a double-blind study of 20 healthy participants with hallucinogen experience, psilocybin (10, 20, 30 mg/70 kg) and DXM (400 mg/70 kg) both increased ratings of overall drug effect, but psilocybin showed dose-related increases in nine domains linked to reinforcing effects—including liking, visual effects, positive mood, insight, social effects, appreciation of beauty, awe, meaningfulness, and mystical experience. For most ratings, the two highest psilocybin doses were significantly greater than DXM, and DXM never exceeded psilocybin. These differences matched participants' desire to take the drug again.
Frontiers in Neuroergonomics
January 20, 2022
Yun Zhou, Frederick S. Barrett, Theresa M. Carbonaro et al.
17 citations
A psychoactive dose of psilocybin (10 mg/70 kg) occupied an average of 39.5% of serotonin 2A receptors in the brains of four healthy volunteers, as measured by PET imaging. The highest occupancy occurred in regions of the default mode network, including the subgenual anterior cingulate and bilateral angular gyri, with values between 63.12% and 74.72%. Individual variability in regional occupancy was marked. These findings support further research into how differences in receptor occupancy relate to psilocybin's acute and lasting effects.
ACS Pharmacology & Translational Science
December 29, 2020
Michael B. Gatch, Adam C. Hoch, Theresa M. Carbonaro
13 citations
Eight novel substituted tryptamines produced hallucinogen-like effects in rats trained to discriminate the hallucinogen DOM from saline. All compounds fully substituted for DOM, with potencies equal to or less than DOM. Four compounds—4-OH-MET, 4-OH-DET, 4-OH-DMT, and 4-AcO-DMT—reduced response rates at fully substituting doses. Because these compounds mimic DOM's discriminative stimulus effects, they may carry similar abuse liability. 4-Acetoxy substituted compounds were less potent than 4-hydroxy ones, and N,N-diisopropyl compounds were less potent than those with dimethyl, diethyl, N-methyl-N-ethyl, or N-methyl-N-isopropyl groups.
Drug and Alcohol Dependence
January 21, 2017
Theresa M. Carbonaro, Matthew W. Johnson, Roland R. Griffiths
3 citations
No Summary
Drug and Alcohol Dependence
December 16, 2014
Theresa M. Carbonaro, Frederick S. Barrett, Matthew P. Bradstreet et al.
3 citations
No Summary
Drug and Alcohol Dependence
October 31, 2015
Theresa M. Carbonaro, Margaret A Klinedinst, Matthew W. Johnson et al.
1 citation
No Summary
Journal of Pharmacology and Experimental Therapeutics
January 25, 2024
Hannah E. Shaw, D. R. Patel, Brenda M. Gannon et al.
Novel arylcyclohexylamine (ACX) analogs of PCP, PCE, and ketamine, which appear on the illicit market, show PCP-like abuse liability and varied toxicities. In mice, PCP-like ACXs were more effective locomotor stimulants than amphetamines, while ketamine-like ACXs were less effective. Adding -Cl, -OH, or -OMe at the 3-position did not affect locomotor effectiveness, but 4-OMe reduced it. Drugs with -OH at the 3-position or -OMe at the 3- or 4-position induced lethal effects. All novel ACXs partially substituted for PCP in rats, and PCP and 3-Cl-PCP caused dose-dependent psychosis-like neurocognitive deficits not seen with cocaine or morphine.
Psychopharmacology
March 1, 2013
Theresa M. Carbonaro, Michael J Forster, Michael B. Gatch
The hallucinogen DiPT, known for causing auditory distortions, produces discriminative stimulus effects in rats that are similar to those of other synthetic hallucinogens like LSD, DOM, and MDMA, but only partially similar to DMT and not similar to methamphetamine. Rats learned to distinguish DiPT from saline in about 60 training sessions. DiPT caused dose-dependent increases in drug-appropriate responding, reaching 99% at the highest dose. The effects began within 5 minutes and faded within 4 hours. The results suggest that DiPT's auditory effects do not make its discriminative stimulus profile distinct from other hallucinogens.