The American journal of drug and alcohol abuse
January 1, 2018
Thomas Kingsley Brown, Kenneth Alper
156 citations
Ibogaine, a plant alkaloid, was associated with reduced opioid withdrawal symptoms and drug use in 30 people dependent on heroin or prescription opioids who had not benefited from other treatments. Withdrawal scores dropped from 31 to 14 within about three days. One month after treatment, half of the subjects reported no opioid use in the previous 30 days. Improvements in drug use, legal, and family or social problems were sustained for up to 12 months, though the strongest effect on drug use was at one month. These findings suggest ibogaine may offer a new model for addiction pharmacotherapy.
Frontiers in Pharmacology
January 4, 2023
Kenneth Alper, Janelle Cange, Ria Sah et al.
39 citations
A single dose of psilocybin reduces voluntary ethanol consumption in male mice for three days afterward, but has no effect in female mice. The reduction is dose-related and occurs at 0.5 mg/kg or higher, but does not persist when ethanol is reintroduced after two days of withdrawal. The effect is not due to altered taste perception, motor effects, or nonspecific changes in drinking behavior. These findings suggest sex-dependent effects of psilocybin on alcohol drinking and indicate that the C57BL/6J mouse may be useful for studying sex differences in alcohol use disorder and the neurobiology of psychedelics.
Frontiers in Pharmacology
August 31, 2018
Kenneth Alper, Bin Dong, Relish Shah et al.
37 citations
A single high dose of LSD (50 μg/kg) reduced alcohol consumption by an average of 17.9% in adult male mice over 46 days, with no change in total fluid intake or activity. A lower dose (25 μg/kg) had no effect. The findings suggest classical hallucinogens warrant further animal research for addiction neurobiology and drug discovery.
PloS one
January 1, 2013
Tamara Antonio, Steven R Childers, Richard B Rothman et al.
36 citations
Iboga alkaloids, including ibogaine, its metabolite noribogaine, and the synthetic compound 18-methoxycoronaridine (18-MC), were tested for their ability to activate the μ-opioid receptor (MOR), a common target of opioid drugs. In rat thalamic membranes, all three compounds acted as antagonists, blocking the receptor rather than activating it, with functional Ke values ranging from 3 μM for ibogaine to 13 μM for noribogaine and 18-MC. None of the compounds stimulated MOR-related G protein activity in cells expressing human or rat MORs, and only limited partial agonist effects were seen in mouse MOR-expressing cells. The findings indicate that an opioid agonist mechanism does not explain these alkaloids' effects on opioid withdrawal, supporting a novel mechanism of action and justifying further search for alternative targets.
Cardiovascular toxicology
January 1, 2016
Kenneth Alper, Rong Bai, Nian Liu et al.
35 citations
Ibogaine, a compound used to treat addiction, can cause dangerous heart rhythm problems by blocking hERG potassium channels. This study measured how strongly several iboga alkaloids block hERG channels in human cells. Ibogaine and its metabolite noribogaine blocked hERG channels with IC50 values around 2-4 µM, while 18-methoxycoronaridine (18-MC), a synthetic derivative, showed much weaker blockade (IC50 >50 µM). Although 18-MC bound to hERG channels with similar affinity as other compounds, it produced substantially less channel blockade. These findings suggest that 18-MC may have a safer cardiac profile than ibogaine, and that the structural differences among iboga alkaloids offer a useful model for studying hERG channel biology.
Journal of ethnopharmacology
February 15, 2012
Kenneth Alper, Maarten E.A. Reith, Henry Sershen
13 citations
Ibogaine, a psychoactive alkaloid from the root bark of Tabernanthe iboga, is used to treat addiction and is a candidate for pharmaceutical development. Its ability to inhibit acetylcholinesterase (AChE) has pharmacological and toxicological relevance. Using Ellman's reagent with physostigmine as a control, ibogaine inhibited AChE with an IC50 of 520 ± 40 μM. This inhibition is physiologically negligible and does not explain functional effects in animals or humans that might suggest involvement of muscarinic acetylcholine pathways.