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A non-hallucinogenic psychedelic analogue with therapeutic potential.

ABSTRACT: The psychedelic alkaloid ibogaine has anti-addictive properties in both humans and animals¹. Unlike most medications for the treatment of substance use disorders, anecdotal reports suggest that ibogaine has the potential to treat addiction to various substances, including opiates, alcohol and psychostimulants. The effects of ibogaine-like those of other psychedelic compounds-are long-lasting², which has been attributed to its ability to modify addiction-related neural circuitry through the activation of neurotrophic factor signalling^3,4. However, several safety concerns have hindered the clinical development of ibogaine, including its toxicity, hallucinogenic potential and tendency to induce cardiac arrhythmias. Here we apply the principles of function-oriented synthesis to identify the key structural elements of the potential therapeutic pharmacophore of ibogaine, and we use this information to engineer tabernanthalog-a water-soluble, non-hallucinogenic, non-toxic analogue of ibogaine that can be prepared in a single step. In rodents, tabernanthalog was found to promote structural neural plasticity, reduce alcohol- and heroin-seeking behaviour, and produce antidepressant-like effects. This work demonstrates that, through careful chemical design, it is possible to modify a psychedelic compound to produce a safer, non-hallucinogenic variant that has therapeutic potential.

SUBMITTER: Cameron LP

PROVIDER: S-EPMC7874389 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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A non-hallucinogenic psychedelic analogue with therapeutic potential.

Cameron Lindsay P LP Tombari Robert J RJ Lu Ju J Pell Alexander J AJ Hurley Zefan Q ZQ Ehinger Yann Y Vargas Maxemiliano V MV McCarroll Matthew N MN Taylor Jack C JC Myers-Turnbull Douglas D Liu Taohui T Yaghoobi Bianca B Laskowski Lauren J LJ Anderson Emilie I EI Zhang Guoliang G Viswanathan Jayashri J Brown Brandon M BM Tjia Michelle M Dunlap Lee E LE Rabow Zachary T ZT Fiehn Oliver O Wulff Heike H McCorvy John D JD Lein Pamela J PJ Kokel David D Ron Dorit D Peters Jamie J Zuo Yi Y Olson David E DE

Nature 20201209 7842

The psychedelic alkaloid ibogaine has anti-addictive properties in both humans and animals<sup>1</sup>. Unlike most medications for the treatment of substance use disorders, anecdotal reports suggest that ibogaine has the potential to treat addiction to various substances, including opiates, alcohol and psychostimulants. The effects of ibogaine-like those of other psychedelic compounds-are long-lasting<sup>2</sup>, which has been attributed to its ability to modify addiction-related neural circu ...[more]

PMID: 33299186

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Project description:IntroductionFew population-based studies have examined associations between psychedelic use and mental health outcomes. This work describes characteristics of exclusive psychedelic mushroom use (referred to as PM use), PMs in combination with other psychedelic substances (multi-psychedelic or MP) use, and non-psychedelic use and explores mental health ratings in non-clinical settings.MethodsThis work uses cross-sectional survey data from American adults collected by Acumen Health Research Institute, including demographic characteristics, general health-related quality of life (Veterans RAND derived mental and physical health composite scores), depression (PHQ 9-item), anxiety (GAD 7-item), comorbid conditions (CCI), health resource utilization, and perceptions, knowledge, and use of psychedelics. Multivariate and descriptive statistics were used to describe participant characteristics. Correlation analysis assessed anxiety and depression scores across groups. Mean anxiety and depression scores were compared using ANOVA and Tukey's HSD. A multivariate linear regression model controlling for past-year depression, past-year anxiety, age, region, ethnicity, sex, educational attainment, employment, and psychedelic use predicted mental health composite scores (MCS).ResultsOf the 6,869 participants included in the dataset, 256 (3.7%) reported using psychedelics in the last 12 months. Of those using psychedelics, 122 (47.7%) reported PM use and 134 (52.3%) reported MP use. All psychedelic users reported lower MCS and higher levels of anxiety and depression relative to non-users (those who said they had not used psychedelics in the past year). The lowest mental health scores were reported in the MP users followed by the PM users (higher MCS corresponded to better mental health). When controlling for confounding characteristics including past-year anxiety and depression, disparities in mental health scores persisted between those with any psychedelic use and the non-psychedelic group (p<0.001).ConclusionThis paper extends previous work describing the association between psychedelic use and mental health, controlling for confounding mental health factors such as comorbid anxiety and depression. These results suggest psychedelic users may have poorer mental health than their non-using counterparts in certain contexts and emphasize the need for future research in this field. Both non-adjusted and adjusted analyses demonstrate lower mental health scores for PM and MP users relative to non-psychedelic users. These differential effects highlight the need for further detailed, population-based research on the use of exclusive psilocybin and on psychedelics in combination.

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A non-hallucinogenic psychedelic analogue with therapeutic potential.

Publications

A non-hallucinogenic psychedelic analogue with therapeutic potential.

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