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.
Neuropharmacology
December 1, 2015
Émeline L. Maillet, Nicolas Milon, Mari D. Heghinian et al.
59 citations
Noribogaine, the main human metabolite of the anti-addictive substance ibogaine, reaches brain concentrations up to 20 μM after a therapeutic dose. Binding experiments and computational simulations indicate it may bind to the orthosteric morphinan site of opioid receptors. Noribogaine is a weak mu opioid receptor antagonist (Ke=20 μM at both G-protein and β-arrestin pathways) but a G-protein biased kappa opioid receptor agonist: 75% as efficacious as dynorphin A at stimulating GDP-GTP exchange (EC50=9 μM) yet only 12% as efficacious at recruiting β-arrestin. It also functionally inhibits dynorphin-induced kappa β-arrestin recruitment (IC50=1 μM), more potent than its G-protein agonism.
Journal of psychopharmacology (Oxford, England)
July 1, 2016
Deborah C. Mash, Barbara Ameer, Delphine Prou et al.
29 citations
Oral noribogaine dose dependently reduced naloxone-precipitated morphine withdrawal signs in mice by up to 88% with an ED50 of 13 mg/kg. Noribogaine showed high brain penetration with a brain/blood ratio of 7±1 across all doses tested. In rats, noribogaine up to 100 mg/kg did not produce conditioned place preference, indicating it is not perceived as a hedonic stimulus. Retrospective review of ibogaine studies suggests that differences in route of administration and testing time explain literature discrepancies. Noribogaine, not ibogaine, likely mediates withdrawal-blocking effects and may offer a non-addictive alternative to opiate replacement therapies.
Journal of psychopharmacology (Oxford, England)
June 1, 2015
Qing Chang, Taleen Hanania, Deborah C. Mash et al.
26 citations
Noribogaine, a drug that acts on opioid receptors, nicotinic receptors, and serotonin transporters, was tested for its ability to reduce nicotine self-administration in adult male rats. After training to self-administer nicotine intravenously, rats received oral doses of noribogaine (12.5, 25, or 50 mg/kg), vehicle, varenicline, or saline. Noribogaine dose-dependently decreased nicotine self-administration by up to 64% compared to saline-treated levels, matching the effectiveness of 1.7 mg/kg varenicline. At the highest dose, noribogaine reduced food pellet self-administration by only 23%, indicating greater specificity for nicotine. The findings suggest noribogaine may be a promising treatment for nicotine dependence.
Journal of Psychopharmacology
March 1, 2022
Neiloufar Family, Peter S. Hendricks, Luke T. J. Williams et al.
23 citations
LSD doses of 50, 75, and 100 micrograms are tolerable and safe in healthy adults when administered in a novel group-based intervention paradigm with one attendant per participant. Thirty-two adults (mean age 28.8 years) received LSD or placebo across open-label and double-blind designs. No serious adverse events occurred; 28% of participants reported at least one mild expected adverse event and one moderate event. Peak blood plasma levels appeared 1.2 to 2 hours after administration, with an apparent half-life of 2.8 to 4.3 hours. LSD produced greater subjective effects than placebo, including mystical-type experiences. Further research is needed in clinical populations.
Behavioural Brain Research
July 14, 2017
Allan V. Kalueff, Aleksandra Kaluyeva, Émeline L. Maillet
21 citations
Noribogaine, the main psychoactive metabolite of ibogaine, produces robust anxiolytic-like behavior in adult zebrafish without affecting locomotion. In a 5-minute novel tank test following acute 20-minute immersion in 1, 5, or 10 mg/L noribogaine, treated fish spent more time and made more transitions to the top half compartment and showed fewer freezing bouts compared to controls. These results indicate noribogaine modulates components of the acute stress response related to emotionality and anxiety, suggesting it may be a potentially useful non-sedative anxiolytic agent.
The FASEB Journal
April 1, 2015
Émeline L. Maillet, Nicolas Milon, James A. Fishback et al.
1 citation
Noribogaine, the primary metabolite of the anti-addictive substance ibogaine, modulates opioid receptors in ways that may explain its therapeutic effects. At mu-opioid receptors, noribogaine acts as a moderately potent antagonist of both G-protein and β-arrestin signaling pathways. At kappa-opioid receptors, it is a partial agonist of the G-protein pathway, activating at 75% the maximal efficacy of Dynorphin A with a potency of 9 µM, while poorly activating the β-arrestin pathway. Noribogaine functionally inhibits Dynorphin A-induced β-arrestin recruitment at physiologically relevant concentrations, with an IC50 of 1.45 µM. Computational simulations suggest noribogaine binds to the orthosteric morphinan binding site.
The FASEB Journal
April 1, 2015
Émeline L. Maillet, Qing Chang, Nicolas Milon et al.
Noribogaine, a drug that acts on opioid receptors, nicotinic receptors, and serotonin transporters, was tested for its effects on nicotine dependence. It inhibited several types of nicotinic acetylcholine receptors, including α3β4 and α7. In a rat model of nicotine self-administration, noribogaine dose-dependently reduced nicotine intake by up to 64% compared to saline-treated rats, an effect comparable to the approved smoking cessation drug varenicline. These results suggest noribogaine may have potential for treating smoking cessation, substance abuse, and anxiety disorders.